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Mice
129-E Mouse AKR MouseB6C3F1 Mouse B6D2F1 (BDF1) MouseBALB/c Mouse BALB/c Nude MouseC3H Mouse C57BL/6 MouseC57BL/6-E Mouse CB6F1 MouseCD-1™ Mouse CD-1™ Nude MouseCD2F1 (CDF1) Mouse CF-1® MouseDBA/2 Mouse Fox Chase CB17™ MouseFox Chase SCID® Mouse Fox Chase SCID® Beige MouseFVB Mouse NIH-III Nude MouseNOD SCID Mouse NU/NU Nude MousePGP Mouse (P-glycoprotein Deficient) THE POUND MOUSE™SCID Hairless Outbred (SHO™)Mouse SJL-E MouseSKH1-E Mouse Swiss Webster (CFW®) MouseTransgenic Mice
Rats BDIX Rat Brown Norway RatBuffalo Rat CD® RatCD® Hairless Rat CDF® RatCopenhagen Rat Dahl/SS RatF344 (SAS FISCH) Rat FHH RatGK Rat JCR RatLewis Rat Long-Evans RatNoble Rat Obese Prone RatObese Resistant Rat PCK RatRNU Nude Rat SHHF RatSHROB Rat SHR RatSprague Dawley® Rat SS-13BN RatStroke Prone (SHR/SP) Rat Wistar Furth RatWistar Han Rat Wistar RatWKY Rat ZDF RatZSF1 Rat Zucker Rat
Rabbits NZW RabbitGuinea Pigs
Hartley Guinea PigIAF Hairless Guinea PigHamsters LVG HamsterGerbils Mongolian Gerbil
disease models overview
disease models: diet disease models by indication informationbaseline data overviewbaseline data by strain baseline data by parameterhealth reportsoverview North America Europe & Asiamore... ordering information on-line literaturefrequently asked questions
Thoracic viscera in situ
A. Mice
• ORIGINProgenitors: two male and seven female albino Swiss mice derived from a non-inbred stock in the laboratory in Switzerland.
• To the United States by Dr. Clara Lynch of the Rockefeller Institute in 1926.
• The Hauschka Ha/ICR stock was initiated in 1948 at the Institute for Cancer Research (ICR) in Philadelphia from “Swiss” mice of Rockefeller origin.
• To Charles River in 1959. • CD-1（ICR），and registered the trade marks CD-1
1. ICR
A. Mice1. ICR
• CD-1：是ICR小鼠的升级替代品系。
• ICR小鼠因不同地域饲养而引起的不同封闭群之间的差异，Charles River将世界各地繁殖的CD-1种群按计划定期轮换，形成了具有国际遗传学标准的CD-1 IGS（International genetic standard）小鼠。这也是CD-1小鼠特有的优势
• COAT COLORWhite (albino); carries black agouti behind its albino gene
• RESEARCH APPLICATIONgeneral multipurpose model, safety and efficacy testing, aging, surgical model, pseudopregnancy
• 该小鼠是国际通用的封闭群小鼠, 我国从美国、日本、英国、瑞士等国引进的ICR，各群体之间在遗传特性方面不可避免地出现了一些差异，在应用时应注意。
• 肿瘤研究是ICR小鼠的重要用途所在。例如：华蟾素与紫杉醇合用对S180小鼠移植瘤作用的实验研究
• 1. ICR– Swiss, 1926,美国Rockfeller研究所从瑞士引入白化小鼠培育成瑞士种Swiss小鼠。
– KM小鼠, 1944年3月17日, 汤飞凡从印度Hoffkine研究所引进Swiss小鼠，饲养在中国昆明中央防疫处.
– ICR, Hauschka用Swiss小鼠群以多产为目标，进行选育，Institute of Cancer Researcch分送各国饲养实验，各国称为ICR.
• KM 鼠携带的Mpi-1 ，Es-10 等罕见等位基因实验小鼠中很少见，仅存在于东南亚包括中国某些地区的小家鼠M.m.castaneus和M.M.molossinus的基因库里。Gpt-1 也是KM 鼠所独有．Swiss mice远交群没有。
• 下颌骨形态遗传分析结果说明,来源于Swiss mice种的NIH 鼠与KM 鼠有明显的差异。
• Thy-1，Es-2，Es-10等为KM 鼠和M.m. castaneus所共有，可能KM 鼠已经M.m.castaneus父源污染。
• 五个昆明小鼠封闭群遗传生化位点比较研究• Comparative Studies on the Genetic
Biological Markers of Five Closed Colonies of Kunming Mice
• , 刘双环岳秉飞 , 刘殿峰 , 胡卫平 , 章根木 , 王珑 , 邢瑞昌测定Es3等十三个生化位点的基因型分布.结果不同昆明小鼠种群之间存在差异,需要进一步标准化.
2、 Strain Name: BALB/cByType Inbred Strain
TJL Mating System Sibling x Sibling Species laboratory mouse
H2 Haplotype dGeneration F216 (16-NOV-05)
•①Strain Details
•②Appearance: Albino
Origin1、H.J. Bagg developed the “Bagg
albino” in 1913 from stock from an Ohio pet dealer.
2、Inbred in 1923 by McDowell.3、To Snell in 1932 at F26（ the /c was
added）, then to Andervont in 1935. 4、To NIH( National Institutes of
Health ） in 1951 from Andervont at F72.
5、To Chinese Academy of Medical Sciences, Institute of Laboratory Animal in 1985，at F180.
Immunologic Properties
Point 1Point 1 Point 2Point 2 Point 3Point 3
Susceptible to chronic pneumonia
The production of plasmacytomas on injection with mineral oil.
Excessive production of immunoglobulin after the birth of 6 months, especially IgG1 and IgA
IgE response predictpotentialsensitization
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Physiological properties
Point 1Point 1 Point 2Point 2 Point 3Point 3
higher blood
pressureamyloidosis of spleen
Sensitivity to
radiation
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Incidence of cancer
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Low incidence of mammary tumors （3%）, but sensitive to carcinogenic factors.
Cancer
Cancers often happen in adrenal gland and lung.Incidence of lung cancer in males is 32%, in females is 21%.
Ageing and life-span
2
average life-span = 569～648 days in males= 561～816 days in females
1
higher incidence of heart defects and multiple atherosclerosis in aged mice
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Reaction to Bacteria and Viruses
• Sensitive to MurineTyphoid
• Salmonella C’5• Moderately sensitive
to Measles Virus
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About feeding★ Generally good breeding performance★ Average litter size of 5-7pups and weaning occurs at 19 days of age. ★ Long reproductive age (12 months)★ Better not fed with other inbred mice in the same room
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OthersLow alcohol preference
Resistance to atherosclerosis development when fed an atherogenic diet.
1
2
3
Low incidence of ovarian cysts.
High incidence of cardiac calcification, especially in males.
4
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Research Application
cancer and immunology
hybridomadevelopment
monoclonal antibody
productioninfectious disease
1 2
3 4
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Examples1
Evaluation of efficacy of inactivated Vaccine against foot-and-mouth disease in BALB／c mice
2
.
3
Expression of P-selectindeprivation from the platelets ofasthmatic BALB/c mice
Establishment of BALB／c EndometriosisModel
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Examples4 5 6 7
Effects of tetracyclineon expression profiles of genes associated with lipid metabolism in Balb/c Mouse Liver
To establish neoplasm transplantation models of melanoma in BALB/c mice
Establishing cross tumour cell strain of anti-person earlier T-cell single clone and applying different BALB/c subsystem in mice
Preparation and screening of monoclonal antibody to chloramphenicolwith BALB/c mice
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Monoclonal Antibodies
• RESEARCH APPLICATIONgeneral multipurpose model,
• Aging, behavioral, eye, Cancer, pharmacological, biology
• hybridoma development, monoclonal antibody production, infectious disease
• High IgE level– Animal model ofprotein allergenicity
BALB/c MouseBALB/cAnNCrl
Age(Weeks)
3 W 4W 5W 6W 7W 8W 9W 10W
M 9 -14 14-19 18-23 20-25 21-26 22-27 23 -28 24 -29
F 9 -14 11-16 15-20 16-21 17 -22 18-23 19-24 20-25
Weight
3、Strain Name:BALB/c-nudeAthymic (Nude) Mice
• ① 1962, first noticed because of the absence of fur in a closed, but not inbred, stock of albino mice
BALB/c Nude MouseCAnN.Cg-Foxn1nu/Crl
• ② 1966, the genetics were first described in detail by Flanagan, gave the name nude, genetic symbol nu, to the mutant.
• ③ The nu gene is single autosomalrecessive, the phenotypically normal mice in the same litter proved to be heterozygous.
• ④ Athymic mice– 100% mortality within 25 weeks– 45% dying within 2 weeks of birth.
• ⑤ 1968, Pantelouris– homozygous nu / nu: lacked a thymus– homozygous +/+ – heterozygous nu /+
• ⑥ In 1969, Rygaard– the first report of the immunobiology of the
athymic mutant was published – the first report of a successful
heterothansplantation of a human malignant tumor to athymic mice
a normal thymus.
Normal mice
BALB/c-nu
• The nu gene has been transferred to several strains of inbred mice.
• Strain Name:BALB/c-nude
• 免疫机能低下，外界细菌和病毒侵染发病，需无菌或无特定病原体条件。
• 其寿命与环境控制密切相关– 普通环境，存活14～30天– SPF及无菌条件，寿命达1年以上，最长2年。
• 成年，6－8周龄，较高水平的NK细胞• 幼鼠，3－4周龄，NK细胞活性低下• 年龄增长,裸鼠体内正常T细胞会增加，接种肿瘤实验一般采用4-6周小鼠。
• 用已建株的癌细胞系移植裸鼠移植成功率高于用人癌手术标本移植。美国NCR Gazdar，120例– 体外建立的肺癌细胞系的移植成功率高达90%– 新鲜肺癌实体瘤的裸鼠移植成功率只有40%。– 常用方法
• 4、Strain Name:C57BL• ① Strain Details
Type Inbred StrainTJL Mating
System Sibling x Sibling
Species laboratory mouseH2 Haplotype b
Generation F231 (16-NOV-05)
② Appearance: Black.
C57 Mice from The Jackson Laboratory
leaden (grey)
brown black black
black black
C57BL/6 Is now probably the most widely used of all
inbred strains.
C: Cold Spring Harbor Laboratory57: female No. 57 (male No.52) BL: Black6: SubstrainJ: The Jackson Laboratory
Origin • Mate of female 57 with male
52 from Miss Abbie Lathrop's stock by Dr. CC Little
• substrains 6 and 10 were separated 1937.
• C57BL/NCrl (B6C), from the 32nd generation of the B6N colony at Charles River Laboratory 1974
• B6 introduced to the Institute of Laboratory Animal Science, China from Olac in 1985
↓
silbing×silbing
B6 与 B10• C57BL major substrains
A, GrFa, 6 and 10 • Reasons :
accumulation of new mutations a small ammount of residual heterozygosity
• ⊿H9, Igh2 and Lv loci
• microsatellite markers :D4Mit69, D4Mit71 , D4Mit72
B6 与 B10• Spontaneous MutationB6:
Cdh23ahl:
age hearing loss Nnt:conventional diabetes
B10 TLR lps-del :
LPS response weak
Description• Color: Black a/a • Allele Symbol :homozygous for Cdh23ahl
• Life-span: long-lived: males 878±10 days ; females 794±6 days
• Good breeding performancelonger and more regular oestrus cycle Y from M. musculus domesticus hermaphroditic males and XY females
• Substrains：C57BL/6J 1948; C57BL/6N 1951 ; C57BL/6NCrl 1974
• first high quality draft sequence of the mice genome
Biological features• High locomotor activity
wheel activity， tail rattling • Congenital abnormalities 10%
eye defects, Microphthalmia and anophthalmia , polydactyly and otocephaly 8-20% and hereditary hydrocephalus 1-3%
• preference for alcohol morphine• severe Dermatitis（Myobia musculi）
with intense pruritis lead to self-killing and even death, hair loss
• late-onset hearing cdhahl
• Low tumorgenesis but still permissive background for maximal expression of most mutations Primary Lung cancer 1% in males ,3% in breeding females 0% in vergin females; Lymphatic leukaemial﹤ 2%,
mammary adenocarcinomas﹤1%• high susceptibility to diet-induced obesity,
NIDDM, AS
Anatomy features Organs• Small kidney/body weight ratio • Large thyroid • Small hippocampus• Accessory spleens in about 32% of mice • low bone densityCells• low number of Peyer‘s patches• 11-fold lower of hematopoietic stem cells in
bone marrow than DBA/2) but great delayed senescence
• High total WBC but low RBC count
Diet-induced AS• Methods :
Feed atherogenic diet (1.25% cholesterol, 0.5% cholic acid and 15% fat) for 14 weeks• Lesions
range of 4500 to 8000 um2 atherosclerotic aortic lesions/aortic cross-section. • Genes: Ath1 to Ath8.
Loci on chromosomes 1, 3, 5 and 11 are associated with variation in HDL levels with coordinate expression of cholesterol-7-a hydroxylase
Diet-induced DiabetesMethods:
Feed high-fat diet or simplely high-carbonhydrate for five months
• Features C57BL/6J mice showed normal insulin sensitivity but
impaired insulin secretion, Glucokinase activity Realated genes• Nnt gene Gluchos1（ chromosome 13）:Encode nuclear-encoded mitochondrial proton pump RT-PCR demonstrated exons 7- 11 absent →impaired glucose homeostasis control and reduce insulin secretion Gck gene Gluchos2 (chromosome 11) ：
C-to-G transversion at base 131 of exon 7， silent polymorphism ， lower Glucokinase activity
Hearing loss• Spontaneous auditory
degenerationdegeneration of the organ of Corti, from basal, high frequency region and then proceeding apically by time, thus susceptible to noise induced deaf
• Histopathological changes early hair cell changes including bent and fused late loss swelling of affected dendrites . Major genes : Cdh23ahl
• located Ch10 nea genetic marker D10Mit5.
• a G to A transition at nucleotide position 753 of Cdh23 cadherin
• ③ Origin– Little 1921 – female 57 with male 52: C57BL and C57BR– Female 58 with male 58 : C58.
• ④ Uses– most widely used of all inbred strains– C57BL/6 alone over 14% of occasions on
which an inbred strain is used– genetic background for a large number of
congenic strains covering both polymorphic and mutant loci. F1, Targeted, Congenic
Spontaneous diseaseTumours: Primary lung tumours 1% ~ 3% , Lymphatic leukaemia < 2%, mammary adenocarcinomas< 1% ；Leukaemia 7% ； lipomatous hamartomas or choristomas
Atherosclerosis Diabetes mellitus and HypertensionCongenital abnormalities: eye defects, polydactyly,otocephaly, Microphthalmia, anophthalmia, hydrocephalus,Ocular defects
Spontaneous auditory degeneration
• ⑤ good breeding performance• ⑥ substrains• C57BL/10J substrain is similar to the
C57BL/6J substrain– varying at the H9, Igh2 and Lv loci. – C57BL/10J mice are a valuable
immunological research tool.
• Clarence Little to J.P. Scott (lab code Sc) , from Scott to George Snell (Sn) , to the National Institutes of Health (N), C57BL/10ScSnN , C57BL/10ScN
• Clarence Reeder (Cr) , maintaining, mice distributed from this colony , C57BL/10ScNCr
• Mice of both colonies :– annually,14 biochemical markers– every two years, skin grafting; – C57BL/10ScN, C57BL/10ScNCr, C57BL/10ScCr
are names for the same subline of C57BL/10.
Tlr4– , toll-like receptor 4, deletion– defective lipopolysaccharide response, –Two types of naturally mutant mice,
C3H/HeJ and C57BL/10ScCr, Tlr4 gene deficiency。
– C3H/HeJ mice, a point mutation that causes an amino acid substitution.
– Tlr4lps-n, occurs in most other C3H and C57BL/10 substrains.
• LPS，G- ，细胞壁主要致病成分，导致宿主细胞因子失控性表达，严重的感染和多脏器损伤。
• 对LPS产生耐受性，机体自身重要保护机制，同时也抑制了炎症细胞因子的表达，不利于机体抵御微生物的入侵。理论和实际意义
• 例，单核细胞再次暴露于LPS易导致耐受性产生。脓毒症及脓毒性休克存活患者中提取的单核细胞对LPS也具有耐受的特征，明显减轻“二次打击”带来的损伤，提高脓毒性休克患者生存率和改善预后。– TLR靶点药物研究，热点– 干预TLR信号通路中某些环节，提高脓毒性休克及其他感染性疾病疗效
5、 Strain Name: 129•① Appearance•depends on substrain.• Most carry the white-bellied agouti gene .• Also,some may carry albino •or chinchilla and/or the pink-eyed dilution gene, p.
•② Origin• 1928, Dunn, crosses of coat colour stocks from English fanciers and a chinchilla stock from Castle.
129S1
• 亚系的命名表示方法是在原亲本品系名称的后面加一条斜线“/”，再在斜线下标上适当的亚系符号，亚系符号可分为两类。
– 一类亚系符号是用研究人员或研究机构名称的缩写英文字母，第一个字母须大写，随后字母要小写。
–另一类亚系符号是用阿拉伯数或小写英文字母作为亚系的符号。
Major groups of substrains:• Parental substrains(129P):derived from
the original parent strain由原始的父母代繁衍而得(命名为P)；
• Steel substrains(129S):derived from a congenic strain made by outcrossing to introduce the steel mutation 通过远交引入steel突变的同源导入系繁衍而得(命名为S)；
Major groups of substrains:• “Teratoma " substrains(129T):derived from the
129 congenic that originally carried the teratoma mutation 自身带有畸胎瘤突变（teratoma mutation）的同源导入系繁衍而得（命名为T）；
• "X" substrain (129X): genetically-contaminated substrain 基因污染的亚系（命名为X）。
• revision of the nomenclature of this group of strains
129S2/SvPasCrlVr• 该小鼠品系由Jackson实验室的L.C. Stevens在研究工作中得到，命名为129S2/Sv。
• 二十世纪70年代L.C. Stevens将该品系引入到法国巴斯德研究所J.L. Guenet的实验室Pasteur Inst，命名为129S2/SvPas。
• 1998年11月Charles River引入该品系，命名为129S2/SvPasCrl。
• 2002年维通利华从Charles River引入第8代核心群，命名为129S2/SvPasCrlVr。
• 129S2的基因型为Aw/Aw，表型为white (or light)-bellied agouti
• Leroy Stevens• Two decades• Human disease
129S1/SvImJ
Strain Name: 129S1/SvImJ
Former Name
129/SvImJ
129/SvImJ
129S1/Sv-p+ Tyr+ Kitl+
129S3/SvIm
129S3/SvImJ
•Origin•129S1/SvImJ was derived from 129S1/Sv-+p+Tyr-c KitlSl-J/+ . KitlSl-J, the steel-Jackson mutation is segregating.•This name was later shortened to simply 129/SvImJ. •Subsequently designated 129S3/SvImJ,1999 • This strain was renamed 129S1/SvImJ in February, 2001 to emphasize its relationship to Stock 129S1/Sv-+p +Tyr-c KitlSl-J/+ .
•129S1/SvImJ was developed to serve as a control inbred strain for many of the steel-derived ES cell lines
Reseach ApplicationsThis mouse can be used to support research in many areas including:
Cancer ResearchIncreased Tumor Incidence :
Testicular teratomasLung tumor
Reproductive Biology ResearchGonadal Tumors (testicular teratomas)
(2) Genetics Research129 mice are widely used in the production
of targeted mutations due to the availability of multiple embryonic stem cell lines derived from them.eg.knockout mutation mice
B10.129-H-12b
6、 Strain Name: B6.129-apoE•①Strain Details
•②Appearance: black
Type JAX® GEMM® Strain - CongenicType JAX® GEMM® Strain - Mutant StrainType JAX® GEMM® Strain - Targeted Mutation
TJL Mating System Homozygote x Homozygote Species laboratory mouse
Background Strain C57BL/6 Donor Strain 129P2 via E14TG2a ES cell line
Donating Investigator
Nobuyo Maeda, Univ of North Carolina at Chapel Hill
Generation N12F3 (27-FEB-03)
• Homozygous for defective Apoe gene• Complete absence of apoE glycoprotein
• Plasma lipoproteins in which apoEnormally is an integral part (e.g., VLDL, IDL, HDL) are therefore devoid of this apolipoprotein.
• As a result, Apoe Targeted Mutation Mice show dramatic alterations in lipid metabolism and transport, even on a normal mouse chow diet.
• In normal mice, apoE is made by the liver (as in humans) and into all lipoprotein particles (except LDL),
• Including, intestinal cells, CMs• Liver cells, VLDLs• Metabolic products,IDLs, CMs
remnants• Reverse cholesterol transport, HDLs.
• ApoE is to facilitate binding of lipoproteins to cell surface receptors
• Transfer the particle’s lipid moeity, cholesteryl esters, triacylglycerols, to or from cells.
• Specifically, apoE mediates binding to both LDL and LRP (LDL receptor-related protein) receptors, and possibly the VLDL receptor.
• The absence of apoE has multiple effects on lipid metabolism and transport.
• Normal mice, an abundance of HDL and only trace amounts of lower-density lipoproteins (VLDL, IDL, LDL).
• ApoE Targeted Mutation, 80% of serum cholesterol in lower density lipoproteins, HDL-cholesterol is half the normal level.
• Total cholesterol levels in plasma are up to five times that of normal mice 434 mg/dl versus 86 mg/dl
• Quantity of cholesterol and its distribution among lipoprotein fractions are shifted to a pattern known to be associated in humans with risk of atherosclerosis.
Mice homozygous for the Apoetm1Unc
mutation show a marked increase in total plasma cholesterol levels that are unaffected by age or sex.
Western-type Food动物分组 TC TG GLU HDL LDL
C57BL 3.66±0.27 0.47±0.23 10.14±1.19 2.32±077 1.12±0.25apoE-/- 13.22±0.38* 0.62±0.36 6.86±2.65 2.98±0.67 9.96±0.95**
小鼠品系 性别 TC TG雌性 2.79±0.083 0.75±0.34雄性 2.98±0.57 1.04±0.29雌性 5.81±1.30 0.524±0.21雄性 7.04±0.17 1.20±0.40
apoE-/-
C57BL/6
Normal Diet
• Spontaneous susceptibility to early and extensive development of atheromas regardless of diet.
• Unlike normal mice• Normal mouse chow• 3mon, foam cell
accumulations on their aortic walls
• 8mon, extensive atherosclerotic lesions and severe vessel occlusion
HE×100
No AS plaque As plaque
Fatty streaks in the proximal aorta are found at 3 months of age. The lesions increase with age and progress to lesions with less lipid but more elongated cells, typical of a more advanced stage of preatherosclerotic lesion.
• Normal reproductive performance in both male and female ApoE Targeted Mutation Mice
• No reported difference in body weights or litter size compared to normal mice
• Enrichment of VLDL and IDL particles with apoA-I, apoA-IV, and apoB-48, similar to their distribution in humans who are apoE deficient, and similar to chylomicron remnants
（1）Cardiovascular Research
Lipoprotein profile changes
Vascular Defects
Atherosclerosis
Heart Abnormalities
Hypercholesterolemia
(2) Neurobiology ResearchBehavioral and learnrning DefectsAlzheimer's DiseaseAPOE mutantsNeurodegeneration• Less well understood but
intriguing are possible roles for apoE in nerve regeneration and amyloidprocessing in CNS neuron.
（3）Diabetes and obesity research
(4) Rat / human homologous gene
Alzheimer's Disease
Hyperlipoproteinemia
7、Strain Name: B10.RIII-H2r
Type JAX® GEMM® Strain - CoisogenicType JAX® GEMM® Strain - CongenicType JAX® GEMM® Strain - Major
Histocompatibility CongenicType JAX® GEMM® Strain - Mutant Strain
Species laboratory mouseBackground Strain C57BL/10SnSg
Donor Strain RIII/WyJH2 Haplotype r
Generation F97+15 (06-OCT-05)
•①Strain Details
Strain H-2 haplotype Strain H-2 haplotype Strain H-2 haplotypeA/HeJ a C57BL/KsJ d NZB/B1NJ dA/J a C57BR/cdJ k NZW/LacJ zA/WySnJ a C57L/J b P/J pAKR/J k C58/J k PL/J uAU/SsJ q CE/J k RBF/DnJ unknownBALB/cByJ d C3HeB/FeJ k RF/J kBALB/cJ d C3H/HeJ k RIIIS/J rBUB/BnJ q C3H/OuJ k SJL/J sCBA/CaJ k C3H/HeSnJ k SM/J vCBA/NJ k DBA/1J q ST/bJ kCBA/CaH-T6J k DBA/1LacJ q SWR/J qCBA/J k DBA/2J d 129/J bC57BL/6ByJ b DW/J b 129/ReJ bC57BL/6J b I/LnJ j 129/SvJ bC57BL/10J b LP/J b WB/ReJ jC57BL/10SnJ b MA/MyJ k WC/ReJ j
About Collagen Induced Arthritis(CIA)• Susceptibility to collagen-induced arthritis(CIA), a murine model of autoimmune arthritis, is strongly linked to only two major histocompatibility complex(MHC) haplotypes, H-2q and H-2r.
About Collagen Induced Arthritis(CIA)• In order to identify the determinants of type II collagen (CII) required to induce arthritis in H-2r -bearing mice
• Bl0.RIII mice were immunized with bovine, chick or human CII. Only bovine CII induces significant arthritis and autoantibodies.
About Collagen Induced Arthritis(CIA)• When the major peptides of bovine collagen were isolated and used for immunization, only mice immunized with CB8, representing CII 403-551, developed arthritis.
ORIGINBackground Strain C57BL（/10SnSg）
• Donor Strain RIII（/WyJ）
Allele Symbol Ap3b1pe-11J--- Adaptor-related proteins 3Allele Name pearl 11 JacksonStrain of Origin B10.RIII-H2/(71NS)SnJ
Gene Symbol and Name Ap3b1, adaptor-related protein complex 3, beta 1 subunit衔接因子相关蛋白复合体3，β1亚基
• ② Appearance:• dark grey with much lighter ears, tail, and feet;
black③ Research Applications
• Ap3b1pe-11J related– Dermatology Research
Color and White Spotting Defects – Hematological Research
Platelet Defects (platelet storage pool deficiency) – Internal/Organ Research
Kidney Defects (lysosomal enzyme abnormalities)
• DescriptionThis congenic strain develops chronic and relapsing experimental autoimmune encephalomyelitis (EAE) after immunization with myelin basic protein (MBP).
• Susceptibility is associated with the major histocompatibility complex (MHC) allele, H2r, the T cell receptor V β8 chain, and other non MHC loci.
• This strain also is susceptible to induction of collagen-induced arthritis.
8、 Strain Name: C3H
Type Inbred StrainTJL Mating System Sibling x Sibling
Species laboratory mouseH2 Haplotype k
Generation F255 (16-NOV-05)
•①Strain Details
•②Appearance:agouti.
Origin of the inbred strain
Developed by Strong 1920 from a cross of Baggalbino with DBA male (see CBA) with selection for a high incidence of mammary tumours. 1930,Andervont introduce 4 female and 2 male mices1931,Heston introduce F351951,NIH(National Institutes of Health) introduce F57 from Heston1974,Charles River introduce it and peromfecesarean in 19752001,Vital River introduce this strain from Charles River
Characteristic毕 业 论 文 答 辩
High incidence of mammary tumours
Usually > 90% at one year
Caused by a virus which is passed from mother to offspring through the milk.Fostering of the young or transfer of fertilised ova to a mammary tumour virus-free strain eliminates the virus, and substantially reduces the incidence of mammary tumours.
Characteristic毕 业 论 文 答 辩
High incidence of mammary tumours
Hepatomas
72-91% in males at 14 months, 59% in virgin females, 30-38% in breeding femalessusceptibility being associated with six chromosomal regions
Characteristic毕 业 论 文 答 辩
High incidence of mammary tumours
Hepatomas
Spontaneous mutation
At lipopolysaccharide response locus, making C3H/HeJ miceendotoxin resistant
Highly susceptible to infection by Gram-negative bacteria such as Salmonella enterica.
Characteristic毕 业 论 文 答 辩
High incidence of mammary tumours
Hepatomas
Spontaneous mutation
Others
Hair color agoutiMature period 8-10 wOestrous cycle 4-5dDuration of pregnancy 19-21dForage 5g/100g/dWarter 6-7ml/100g/dWeed out cycle 8-12MTemperature /humidity 19-23℃/30-70%
Diagram
Title
Low intrastrain aggression Low open-field activity .Low open-field defaecation
Add Your Text
High food drive ，but poor performance in food-seeking task
Short time of immobility in a forcedswimming testLow shock-avoidance learning.
Carries the retinal degeneration gene and is capable of pattern discrimination up to 40 days, and brightness discrimination to at least 100 days
Good short- term but poor long-term memory in contrast with DBA/2 Good T-maze learning
Characteristic
Poor water-escape learning.Low radial-arm maze learning
• The unfostered substrains are widely used in cancer research for the sake of their mammary tumours.
• Fostered stock are widely used as a general-purpose strain which is readily available and well known.
• Some substrain differences are large, and can not be accounted for solely on the basis of mutation, and must be ascribed either to substantial residual heterozygosity or genetic contamination.
Characteristic
Major substrains奇特核电形状因子的研究
毕 业 论 文 答 辩
C3H/Bi C3H/HeJ C3H/FgC3H/He
Strong to Bittner1931, toKirschbaum1952. Has 83%mammary tumours in unfosteredbreeders.Low leukaemia
This substrain was passed to Heston in 1941,and is now the most widely distributed of all. Non-fostered substrains have more than 90% mammary tumours by about 11 months. Fostered substrains have a high incidence of hepatomas.
Heston, to Jackson Laboratory in 1947, and now widely distributed. Has poor immune response to endotoxiclipopolysaccharidedue to a B-cell deficit
Origin not known, but has a very high incidence of lymphatic leukaemia
Major substrains
C3HeB/FeJ Primary lung tumours 8% in males, 4% in breeding females and 10% in Virgin females. Lymphatic leukaemia zero.Mammary adenocarcinomas zero in males, 12% in breeding females, 2% in virgin females Ovarian tumours 47% in Virgin and 37% in breeding females, 29% in force-bred females. Hepatomas 91% in breeding males, 58% in Virgin and 30% in breeding females High gross tumour incidence in males
Normal physiology and biochemistry
parameter male femaleRBC 9.63
1E6/μl9.54 1E6/μlMCV 54.75 54.95fl
RDW 12.34%cv 12.52%cvHCT 52.77% 52.27%MCH 16.14pg 16.51pgMCHC 294.9g/l 301.15g/lWBC 6.661E3/μll 7.25
1E3/μlLY% 75.35% 80.08%PLT 169.351E3/
μll607.4 1E3/μlMPV 5.84fl 4.925 fl
PDW 19.08% 18.92%
Normal physiology and biochemistryNormal physiology and biochemistry
Normal physiology and biochemistryNormal physiology and biochemistry
• ③ origin1920, Strong , cross of Bagg albino with DBA male with selection for a high incidence of mammary tumors. – Unfostered substrains , > 90% – Fostering of the young, – Transfer of fertilized ova to a mammary tumor
virus-free strain– All `SPF' stock will be free of this virus.
• ④ Uses– Now among the most widely used of all
mouse strains. – unfostered substrains are widely used in
cancer research – Fostered stock are widely used as a general-
purpose strain – be careful in behavioural studies, since it
carries the rd (retinal degeneration) gene and is blind after about 6 weeks.
9、 Strain Name: KK
•①Strain Details
•②Appearance:albino
Type Inbred StrainTJL Mating System Sibling x Sibling
Species laboratory mouseH2 Haplotype b
Generation F103 (16-NOV-05)
• ③ Origin: – K. Kondo 1944 from Japanese dealer stock
(Kasukabe group). Some substrains carry the yellow (Ay ) gene.
• ④ Uses– as a model of noninsulin dependent
diabetes mellitus, type 2. – obesity is induced by nutrition – Moderate obesity (mature weight about 45 g)
occurs by about 2 months and stabilises by 4-5 months.
10、 Strain Name: FVB•①Strain Details
•②Appearance:albino
Type Inbred StrainTJL Mating System Sibling x Sibling
Species laboratory mouseH2 Haplotype q
Generation F95 (16-NOV-05)
Origin
• Swiss mice established at the National Institutes of Health in 1935. In 1966 two strains (HSFS/N and HSFR/N) were selected for sensitivity and resistance, respectively, to challenge with histamine following pertussis vaccination.
• Homozygous mice were then inbred as strain FVB, without further selection for histamine sensitivity.
Strain origin
two strains (HSFS/N and HSFR/N) were selected 热休克因子
•单击输入文字内容•单击输入文字内容•单击输入文字内容
FVB/N mice were imported from NIH to Dr. Taketo at The Jackson Laboratory
1966 1970s 1988
at the 8th inbred generation of HSFS/N were found to carry the Fv1b allele
Strain characteristics
1 32
Higher than average activity, anxiety, and basal body temperature
Low stress-induced hyperthermia
Good reproductive performance with large litters
4 65
Early onset retinal degeneration
Sensitive to the B strain Friend leukaemia virus
Other characteristics
Genetics Research
Research applications
Retinal Degeneration
Immunology and Inflammation Research
Retinitis pigmentosa, autosomalrecessive
Pde6brd1
the nascent outer segments and the rod cells degenerate rapidly
a few cones are still present
retinal degenerationand having some visual capacity
2 base "TA" deletion
the creation of a stop codon
macrophages do not secrete C5
C5 deficient，Immuno-deficiency
• ③ Origin: Outbred N:GP (NIH General Purpose) Swiss mice established at the NIH in 1935. – Carry the Fv1b allele for sensitivity to the B
strain of Friend leukaemia virus. – Homozygous mice were then inbred as strain
FVB• ④ Uses
– Fertilized eggs contain large and prominantpronuclei which facilitate the microinjection of DNA
– a vigorous reproductive performance with large litters
11、 Strain Name: FVB-TgN
Type JAX® GEMM® Strain - Mutant StrainType JAX® GEMM® Strain - Transgenic
Species laboratory mouse
Donating Investigator Robert Callahan, NIHGeneration N?+3F7pN1
•①Strain Details
•②Appearance:albino•FVB/WAP/Int3
•Whey acidic protein
Transgene Detail• Symbol : Tg(WapNotch4)10Rnc• Name：Transgene insertion 10, Robert
Callahan• MGI ID ：1930202• Synonyms : Tg(WapInt3)10Rnc, WAP/Int3,
Wap-int3 tg• Transgene : Tg(WapNotch4)10Rnc• Genetic Position : ChrX , Syntenic
Notch4• Synonyms : Int3, Int-3, N4• Feature Type : protein coding gene• Location : Chromosome 17
Transgene description• Transgene Type : Transgenic (random,
expressed)• Mutation : Insertion(The transgene insert
consisted of the mouse whey acidic acid promoter and the portion of the Notch4 gene encoding the intracellular domain. Wap promoter activity is restricted to the secretory mammary epithelial population. Four founder mice were identified. One line established from founder 10. Transmission analysis indicates that the transgene inserted into the X chromosome.)
Description
• In transgenic mice carrying the WAP/Int3 construct, mammary ductal growth was unaffected in virgin females, but growth and differentiation of secretory lobules during gestation was profoundly inhibited.
Description• Mammary dysplasia and tumorigenesis
occurred in all breeding females by 25 weeks of age.
• In non-breeding WAP/Int3 females mammary tumor incidence also reached 100% but only after 70 weeks.
• The WAP/Int3 mammary tumors were highly malignant and most tumor-bearing females, irrespective of breeding history developed metastatic lung lesions.
Description
• FVB/WAP/Int3 females are unable to lactate. This phenotype is different from that of the FVB-TgN(MMTVInt3)3Rnc strain mice.
• In virgin and multiparous mice of that strain, mammary ductal growth and secretory lobule development were both curtailed. Mammary adenocarcinomas are observed as early as 7 weeks, and salivary adenocarcinomas were also observed. Males were sterile.
Description
• Differences in the phenotype are attributed to the tissue-specific promoters used. The WAP promoter directs expression of the transgene to the secretory epithelium, whereas the MMTV LTR is more widely expressed and at an earlier stage of mammary ductal development.
Phenotype Informationendocrine/exocrine gland phenotype
• abnormal mammary gland growth during pregnancy – Gestating females exhibit abnormal
development of secretory lobules. However, mammary ductal growth is unaffected in virgin females
– Pregnant and postpartum mammary glands show dysplastic ducts and poorly formed alveolar buds
– In ducts of postpartum females, the luminal epithelial cells appear condensed and moribund
Phenotype Informationendocrine/exocrine gland phenotype
• lactation failure– Parous females fail to lactate
• increased lung tumor incidence – most tumor-bearing females, irrespective of
breeding history, develop metastatic lung tumors
• mammary adenocarcinoma – all virgin and multiparous females develop
mammary tumors, with a 50% incidence of tumors in virgins at 11 months of age and in breeding females at 5 months
Phenotype Informationtumorigenesis
Application
• Study of tumorigenesis• Breast cancer metastasis mice model• Mice tumor model can simulate the pathophysiological
process of human tumors to a large extent.
• Development of targeted drugs
ApplicationModels of breast carcinomas
• Models of breast carcinomas help to reveal the mechanisms of breast cancer metastasis.
ApplicationModels of breast carcinomas
• Insertional mutation of the Notch4 gene, a member of the Notch gene family, is frequently associated with primary mouse mammary tumors induced by the mouse mammary tumor virus (MMTV).
• A major consequence of these mutations is the production of a shortened 2.4-kb tumor specific Notch4 RNA transcript that encodes the entire intracellular domain of the Notch4 protein.
ApplicationModels of breast carcinomas
• Previous studies have demonstrated that mammary gland development and function was severely impaired in transgenic mice expressing the truncated Int3 gene product from the MMTV viral promoter.
• FVB/WAP/Int3 • FVB-TgN(MMTVInt3)
– promoter directs expression of the transgeneto the secretory epithelium
– widely expressed and at an earlier stage
12、The Severe Combined Immunodeficiency (scid) Mutation
• History• Four littermates of the C.B-17 inbred strain
(BALB/c.C57BL/Ka-Igh-1b/Icr N17F34) – lack detectable IgM, IgG1, and IgG2a – lack both T and B cells resulting in a disease
similar to severe combined immunodeficiency as reported in humans.
– The mutant locus, scid , mouse chromosome 16
13、 Strain Name: NOD
•① Strain Details
•② Appearance•albino
Type Inbred Strain
TJL Mating System Sibling x Sibling
Species laboratory mouse
H2 Haplotype g7
Generation F118 (16-NOV-05)
• ③ Origin– outbred Jcl:ICR mice, in Japan– F6, an elevated fasting blood glucose level in
cataract-free mice.– At F13, the NOD progenitors were separated
from what is now the NON/Shi strain.• NON/Shi strain, High fasting blood glucose levels• NOD progenitors at F13 and later , a normal fasting blood
glucose level.– At F20, in 1974, a female in the
“normoglycemic” line spontaneously developed overt insulin-dependent diabetes mellitus with insulitis (IDDM).
– Selective breeding of the progeny of this diabetic female produced the nonobesediabetic (NOD) strain.
• ④ Uses• homozygous for hearing loss mutation• which on this background results in progressive
hearing loss that is already severe by 3 months of age.
• Developmental Biology ResearchLymphoid Tissue Defects (hematopoietic defects)
• Diabetes and Obesity ResearchHyperglycemia HypoinsulinemiaImpaired Wound Healing Islet Transplantation Studies Type 1 Diabetes (IDDM)
14、Strain Name: NOD.CB17-Prkdcscid/J•①Strain Details
•②Appearance: albino
Type JAX® GEMM® Strain - CongenicType JAX® GEMM® Strain - Mutant Strain
TJL Mating System Homozygote x Homozygote Species laboratory mouse
Background Strain NOD/LtSzDonor Strain C.BKa-Ighb/IcrSz (C.B-17)
H2 Haplotype g7
Generation N10F55 (16-NOV-05)
•③ Origin•Prkdcscid , colony of BALB/c-Ighb (C.B-17)
NOD/Lt ♀× C.B-17-Prkdcscid♂
• ↓
•F1/N1 Prkdcscid+ ♂ × NOD/Lt ♀•10 backcrosses •to NOD/Lt ↓• N10 • ↓b × s inbreeding• homozygous Prkdcscid
• ④ NOD-scid mice– an absence of functional T cells and B
cells – no detectable IgM, IgG1, IgG2a, IgG2b,
IgG3, or IgA– NOD/LtSz-Prkdcscid mice are both
insulitis- and diabetes-free throughout life
• ⑤ Uses– serve as a diabetes-free control for
comparison to NOD/LtJ mice ,thymiclymphomas limit the mean lifespan to only 8.5 months under specific pathogen-free conditions.
– an excellent host for xenografts– also as a source for insulitis-free islets.
15、 Strain Name: NON
•①Strain Details
•②Appearance:albino
Type Inbred StrainTJL Mating System Sibling x Sibling
Species laboratory mouseH2 Haplotype nb1
Generation F116 (16-NOV-05)
•③ Origin•A non-diabetic substrain with the same origin as NOD.•The name was derived from "Non-Obese Non-diabetic"
• ④ Uses• NON/LtJ mice should not be
considered "normal.“• They carry the retinal degeneration
(Pdeb) mutation and exhibit certain tendencies toward autoimmune disease.
16、 Strain Name: CBA
Type Inbred StrainTJL Mating System Sibling x Sibling
Species laboratory mouseH2 Haplotype k
Generation F165
•①Strain Details
•②Appearance:agouti.
• ③ origin1920, Strong , cross of a Bagg albino female and DBA male.
• CBA was selected for a low mammary tumour incidence
• C3H for a high incidence
• ④ substrains– Differences between substrains are probably
too large to be accounted for by mutation, and some degree of genetic contamination in the past is probable.
• CBA/Ca or CBA/H – Strong, to Jackson Laboratory, to Haldane
and Gruneberg in 1932. To Carter 1947 and Harwell 1954. This substrain used in most British research.
17、 Strain Name: MRL/MpJ
•①Strain Details
•②Appearance:albino, unaffected .
Type Inbred StrainTJL Mating System Sibling x Sibling
Species laboratory mouseH2 Haplotype k
Generation F129 (16-NOV-05)
• Inbred Strains of Mice: MRL
•• MRL/MpJMRL/MpJ--FaslprFaslpr
Origin of the MRL：Type: Inbred StrainType: Inbred Strain
Mating System:Mating System: Sibling x Sibling F129 (16-NOV-05）
Species:Species: laboratory mouse
Appearance:Appearance: albino
Genotype:Genotype: a/a Tyrc/Tyrc Fas+/Fas+
Composite Genome:Composite Genome: LG (75%), AKR/J (12.6%), H (12.1%) and
C57BL/6 (0.3%)
Mutated strains:Mutated strains: MRL/MpJ-Faslpr
Biological features:Remarkable tissure regeneration abilityRemarkable tissure regeneration ability：
myocardium
C57Bl/6 mouse [control]
Pancreatitis and Pancreatitis and sialoadenitissialoadenitis:（seven months）Therapy: allogeneic foetal thymus (C57BL/6) +
foetal bone marrow or hematopoetic cells
DrasticDrastic thymicthymic involutioninvolution
Application of MRL/Mp：Immunology and Inflammation Immunology and Inflammation ResearchResearch
1.Sjogren1.Sjogren syndromesyndrome2.autoimmune pancreatitis and 2.autoimmune pancreatitis and sialoadenitissialoadenitis3.experimentally3.experimentally induced rheumatoid induced rheumatoid arthritisarthritis44. lupus . lupus erythematosuserythematosus
Internal/Organ ResearchInternal/Organ ResearchWound Healing (enhanced)Wound Healing (enhanced)
Neurobiology ResearchNeurobiology ResearchVestibular and Hearing Defects Vestibular and Hearing Defects
SensorineuralSensorineural ResearchResearchVestibular and Hearing DefectsVestibular and Hearing Defects
LupusLupus--like disease like disease ::transposable element ETn and Fas gene
Enlargement of the lymph nodes and Enlargement of the lymph nodes and autoimmunityautoimmunityImmune complexes: Immune complexes:
especially in renal glomerulus (3 months)
VacualizaionVacualizaion of the of the thymicthymic epitheliumepitheliumIncrease: Increase:
macrophages, interdigitating cells, cystic cavities, plasmocytes and mastocytes
Interstitial fibrosis and arteriosclerosisInterstitial fibrosis and arteriosclerosisDie at 14Die at 14--16 weeks of age 16 weeks of age
Application of MRL/MpJ-Faslprlpr：
Model of human Model of human Sjogren'sSjogren'ssyndrome:syndrome:Lacrimal gland inflammatory lesions
Research for arthritis:Research for arthritis:mild spontaneous arthritis+Freund‘s
adjuvant
• ③ Origin: – 1960 , crosses of standard inbred strains. – genome composition of LG (75%), AKR/J
(12.6%), C3H (12.1%) and C57BL/6 (0.3%).– 12th. generation of b x s, lpr
(lymphoproliferation) mutation – Homozygotes: MRL/Mp-lpr
• enlargement of the lymph nodes• autoimmunity• die at 14-16 weeks of age.
• ④ Uses• heightened wound healing• MRL/Mp-+/+ mice, 7 months of age
– pancreatitis – sialoadenitis– drastic thymic involution. – Transplantation of allogeneic foetal
thymus(C57BL/6) plus foetal bone marrow or hematopoetic cells
– Results:• normal T and B cell function• pancreatitis and sialoadenitis fully corrected.
18、 Strain Name: DBAType Inbred Strain
TJL Mating System Sibling x Sibling Species laboratory mouse
H2 Haplotype qGeneration F192 (16-NOV-05)
•①Strain Details
•②Appearance:dilute brown , •rey: a,b,d.
• ③ Origin:1909, Little from stock segregating for coat colour,oldest of all inbred strains of mice.
• In 1929-30, crosses , between substrains, – new substrains: substrains /1 and /2. – DBA/1 and DBA/2 differ at least at loci: Car2,
Ce2, Hc, H2, If1, Lsh, Tla, and Qa3.
– Differences too large , mutation, substantial residual heterozygosity ,
– different strains , not substrains of the same strain
– listed separately. • unfostered substrains carry the mammary
tumour virus and have a high indicence of mammary tumours.
19、 Strain Name: SAMP11Type Inbred Strain
TJL Mating System Sibling x Sibling
Species laboratory mouseoriginate AKR/J mice
Generation F192 (16-NOV-05)
•①Strain Details
•②Appearance:dilute brown , •Albino: a,B,c
• Substantial substrain differences, accounted for genetic contamination , by random mating.
• International distribution, ranks about eighthin frequency of use – In cancer research, high leukaemia incidence– In immunology, a source of the Thy1.1 (theta
AKR) antigen. • Viraemic from birth, the ecotropic retrovirus
AKV express in all tissues– Copies are integrated into the genome
• AKR/J crossed (?) with mice of an unknown strain, followed by sib mating
• The Senescence accelerated mouse,SAM– Nine Senescence accelerated
mouse/prone(SAMP) strains– Three senescence accelerated
mouse/resistance(SAMR) strains.
SAMP1
Pathologic phenotypesAfter 4-6 months old, SAM rapidly
emerging all the aging characteristics:Move slowly, activity decreased, shed,
a skin ulcer, changes around the eyelids, eyes fissile small ,corneal ulcers, cataracts, curved spine, senile osteo-porosis, brain atrophy , deficits in learning and memory, emotional disorder etc.
Drug researchSAM mice can naturally occur diseases of the
elderly, thus it is closer to clinical .
In Chinese medicine,the Japanese scholar foundthat feeding 10% red ginseng have the role of stimulating nerve growth factor in SAMP8 submandibular gland.
Drug researchSAM mice can naturally occur diseases of the
elderly, thus it is closer to clinical .
Food containing 8% Modified feed Guipi soup can improve SAMP8 learning and memory impairment.
Crown granules dissolve in water feeding material can reduce lipid peroxidation levels, the increased activity of SOD, showed anti-aging effects.
1. Outbred Stocks of Rats: Wistar
• The Wistar Institute was named in honor of a physician, Dr. Caspar Wistar(1761-1818).
• The first rats brought to the Wistar in 1906 by Donaldson were presumably housed in the museum building.
RatsRats
• In 1918 , Cottonseed meal was introduced into the diet, many rats died or ceased breeding, gossypol toxicity.
• To meet demands of the Institute’s investigators, rats were purchased from outside sources, brought into the facility
• A strain of albino rats developed at the Wistar Institute but which has spread so widely to other institutions that there is probably marked dilution of the strain.– Data
Wistar Kyoto outbred rats Wistar Kyoto intbred rats
Application
• Insulin resistance wistar rat model. • Drugs’ effects of diabetes rat’s
glycometabolism and lipometabolic• The effects of steep pulse electric field
to bearing cancer Wistar rat immunologic function .
• Hypo-immunologic function Wistar rat candida pneumonia model .
RatsRats2. Outbred Stocks of Rats: Sprague-Dawley
Mr. Robert Worthington Dawley (1897-1949), a physical chemist at the University of Wisconsin. In naming the strain, he simply combined the maiden name (Sprague) of his wife and his own name to form Sprague-Dawley. Sprague-Dawley, Inc
• The precise origin of “Sprague-Dawley rat” appears to be lost in uncertainty. – A male rat: exceptional size, and vigor,
half-white– A white female: probably from Wistar
• The male and his white female offspring for seven successive generations
• After his death, his white offspring were inbred, the best ten were combined.
Selection was made to retain or acquire characteristics of high lactation, rapid growth, vigor, good temperament, and high resistance to arsenic trioxide.
APPLICATIONDrug research: drug safety evaluation
tests; Pharmacodynamic Study( blood pressure and vascular resistance is sensitive to
drug) Behavioral research（easy to adapt to the new
environment)Oncology Research(induce tumor, artificial
transplant tumor)Endocrine studies(pituitary - adrenal system
developed)Infectious diseases research( for caused by
infectious diseases and microbiology)
APPLICATIONNutrition and Metabolic Diseases Research
(rat is the first study of nutrition for the experimental animals ,VitD )
Hepatic scientific research (rat hepatic resection of 60% -70%, there are still regeneration)
Breeding Research (rats has larger shape than mice, suitable for tubal, ovariectomy, genital mutilation and other experimentals)
Genetics research (the rat genetic disease has the similar performance with people)
Gerontology research, and radiology research on Chinese medicine (aged rats)
Comparison Between Sprague-Dawley and Wistar Rat In-Vivo Pharmacokinetics and In-Vitro Metabolic Stability with Selected Compounds• 2009 AAPS Annual Meeting and Exposition 11/7/2009 - 11/12/2009• .Tracks:Contributed Papers: Pharmacokinetics/Pharmacodynamics / PreclinicalDate/Time:Thursday, November 12, 2009
8:00 AM - 12:00 PM• Higher mortality rates for Sprague-Dawley (SD) rats have been observed in long term non-clinical toxicology and carcinogenicity studies
compared to Wistar-Han (Wistar) rats. This has resulted in several pharmaceutical companies recently switching to Wistar rats for these studies. A review of the literature indicated that there was limited information comparing the in-vivo pharmacokinetic and in-vitro metabolism data for these two strains of rats. The purpose of this work was to determine if there are differences between SD and Wistar rat in-vivo pharmacokinetics and in-vitro metabolic stability data. Six structurally diverse acidic and basic compounds (zoniporide, diclofenac, zomepirac, Pfizer compounds A, B, C) were selected for this investigation. The compounds were administered intravenously (2.0 or 2.5 mg/kg) and orally (2.0 or 10 mg/kg) to SD and Wistar rats. Plasma and urine samples were collected after a single dose at predetermined time-points (plasma) and time-intervals (urine) over a 24 hour period and analyzed by HPLC/MS/MS. Pharmacokinetic parameters for each compound were determined for both strains. Metabolic stability studies were conducted on all six compounds at 1 uM in SD and Wistar microsomes (0.5 mg/mL protein concentration). Three compounds (zoniporide, compounds B & C) known to be aldehyde oxidase (AO) substrates were also analyzed in SD and Wistar S9 (2.5 mg/mL protein concentration) with and without NADPHand UDPGA co-factors. The in-vivo PK and bioavailability values obtained after intravenous and oral administration were comparable between the SD and Wistar rats (< 2-fold) for all six compounds. Similar in-vitro microsomal stability results from both strains were also obtained for the six compounds. However, zoniporide had a twenty five fold lower half-life in Wistar S9 compared to the SD S9 without cofactors. Since zoniporide in-vivo clearance exceeds hepatic blood flow, the overall in-vivo PK parameters were similar for both strains. Overall, there are no significant strain differences between SD and Wistar rats with in-vitro metabolic stability and in-vivo pharmacokinetics based on the studies conducted with these six compounds.
• Six structurally diverse acidic and basic compounds (zoniporide, diclofenac, zomepirac, Pfizer compounds A, B, C)
• administered intravenously (2.0 or 2.5 mg/kg) and orally (2.0 or 10 mg/kg) to SD and Wistar rats.
• Plasma and urine samples were collected after a single dose at predetermined time-points (plasma) and time-intervals (urine) over a 24 hour period and analyzed by HPLC/MS/MS.
• Metabolic stability studies were conducted on all six compounds at 1 uM in SD and Wistar microsomes (0.5 mg/mL protein concentration).
• Overall, there are no significant strain differences between SD and Wistar rats with in-vitro metabolic stability and in-vivo pharmacokinetics based on the studies conducted with these six compounds.
Lipoprotein lipase in developing rat tissues: differences between Wistar and Sprague-Dawley rats
• Biol Neonate. 1993;64(5):295-303.• Galan X, Llobera M, Ramírez I.• Source• Department de Bioquímica i Fisiologia, Facultat de Biologia, Universitat de Barcelona, Espanya.• Abstract• Lipoprotein lipase in animal tissues is known to be affected by fasting, but contradictory results have been
published concerning this effect in particular tissues. For example, we reported that lipoprotein lipase activity expressed in the liver of neonatal rats was either increased or not affected by fasting. To evaluate the influence of the rat strain used as experimental animal model, we studied differences between Wistar and Sprague-Dawley rats in the development and in the effect of fasting on lipoprotein lipase and hepatic lipase activities in tissues of neonatal rats. Beside some minor differences in the development of lipoprotein lipase in some tissues like brown adipose tissue and lungs, we found quite remarkable differences between both strains in the development of lipoprotein lipase and hepatic lipase activities in the liver. In 1-day-old neonates, differences between both strains were also observed in the effect of fasting on lipoprotein lipase activity both in liver and lungs. In the liver of Wistar pups lipoprotein lipase activity was increased by fasting by 350%, but only by 50% in the liver of Sprague-Dawley pups. In contrast, in the lungs of Wistar pups lipoprotein lipase activity was increased by fasting by 280%, but by 580% in lungs of Sprague-Dawley rats. Therefore, our results indicate that quantitative differences exist between Wistar and Sprague-Dawley rats in the regulation of lipoprotein lipase.
• PMID: 8297939
• Lipoprotein lipase in animal tissues is known to be affected by fasting.
• we studied differences between Wistar and Sprague-Dawley rats in the effect of fasting on lipoprotein lipase activities in tissues of neonatal rats.
• Beside some minor differences in some tissues like brown adipose tissue and lungs, quite remarkable differences between both strains in the development of lipoprotein lipase activities in the liver.
• In the liver of Wistar pups lipoprotein lipase activity was increased by fasting by 350%, but only by 50% in the liver of Sprague-Dawley pups.
• In contrast, in the lungs of Wistar pups lipoprotein lipase activity was increased by fasting by 280%, but by 580% in lungs of Sprague-Dawley rats.
• Therefore, our results indicate that quantitative differences exist between Wistar and Sprague-Dawley rats in the regulation of lipoprotein lipase.
Endocrine differences between the Wistar and Sprague-Dawley laboratory rat: influence of cold adaptation• Horm Metab Res. 1983 Oct;15(10):491-8.• Kühn ER, Bellon K, Huybrechts L, Heyns W.• Abstract• Sprague-Dawley (SD) rats kept at room temperature do have a higher growth rate and food conversion compared
to Wistar rats. Mean hormone level in blood samples collected every four hours during a 24 hour period do differ between both strain of rats. So, the mean circulating levels of T3, T4 and corticosterone are significantly lower, whereas prolactin concentrations are higher in SD-rats. Following acute cold exposure comparable increases in plasma T3 and T4 are seen in both strains after 3-5 hours. Prolactin plasma concentrations are decreased after 5 and 9 hours but only in SD-rats, whereas they remain unchanged in Wistars. Acclimation to 4 degrees C during 3 and 8 weeks resulted in a decreased growth rate of the SD-rats, which becomes comparable to Wistar animals, but food conversion is lower and food intake higher in SD-rats. A decrease in circulating levels of T4 is present in Wistars resulting in a significantly lower figure at 8 weeks of cold acclimation, whereas at the same time T3 is increased. Prolactin is decreased in SD-rats and increased in Wistars causing at 8 weeks of cold acclimation higher levels in Wistars. Corticosterone levels remain higher in Wistar rats and are comparable to rats kept at room temperature. It is concluded that the differences in growth rate, food conversion and food intake are related to the endocrine differences and responses observed.
• PMID: 6642409
• Mean hormone level in blood samples collected every four hours during a 24 hour period do differ between both strain of rats.
• So, the mean circulating levels of T3, T4, corticosterone are significantly lower, whereas prolactin concentrations are higher in SD-rats.
• Following acute cold exposure comparable increases in plasma T3 and T4 are seen in both strains after 3-5 hours. Prolactin plasma concentrations are decreased after 5 and 9 hours but only in SD-rats, whereas they remain unchanged in Wistars.
• Acclimation to 4 degrees C during 3 and 8 weeks resulted in a decreased growth rate of the SD-rats, which becomes comparable to Wistar animals, but food conversion is lower and food intake higher in SD-rats. A decrease in circulating levels of T4 is present in Wistars resulting in a significantly lower figure at 8 weeks of cold acclimation, whereas at the same time T3 is increased. Prolactin is decreased in SD-rats and increased in Wistars causing at 8 weeks of cold acclimation higher levels in Wistars. Corticosterone levels remain higher in Wistar rats and are comparable to rats kept at room temperature.
• It is concluded that the differences in growth rate, food conversion and food intake are related to the endocrine differences and responses observed.
Differences between Wistar and SD rats
• Higher mortality rates for Sprague-Dawley (SD) rats have been observed in long term non-clinical toxicology and carcinogenicity studies compared to Wistar-Han (Wistar) rats. This has resulted in several pharmaceutical companies recently switching to Wistar rats for these studies.
• Sprague-Dawley (SD) rats kept at room temperature do have a higher growth rate and food conversion compared to Wistar rats.
3. Inbred Strains of Rats: F344
• Inbr.F155. Albino, c
• F344/Jcr• Curtiss and Dunning 1920 at Columbia University
Institute for Cancer Research.• This is easily the most widely used general-purpose
inbred rat strain, being particularly favoured for cancer research and toxicology
• Considerable background information,spontaneous diseases and response to chemicals. Testicular interstitial cell tumours85% in males
Drugs and chemicals
Susceptible to Resistant to• polybrominated biphynal monocrotaline
and acrylamide tamoxifen• 4-nitroquinoline-1-oxide .• N-methyl-N-nitrosourea• hydroquinone(males)• kainic acid
□
4. Inbred Strains of Rats: WKY
• Inbr. F46 (N) . Albino, c
• 1971 from outbred Wistar stock from Kyoto School of Medicine.
• Inbred as a normotensive control strain for SHR, though there is some controversy about the validity of such use• Large genetic differences using restriction
fragment length polymorphisms between WKY and SHR
• A high incidence of a range of cardiac abnormalities in WKY/NCrj substrain rats
5. Inbred Strains of Rats: SHR• Inbr. F70 (NIH 1989). Albino, c. • Origin: 1963, Okamoto,
outbred Wistar Kyoto rats. – A male, mild hypertension– A female, high blood pressure. – Brother x sister, selection for
high blood pressure• A number of sublines have
been developed: SHRSP– Males, 12 weeks of age,
average systolic blood pressures > 200 mmHg.
– Normal wistar: 100-120, this lab
• Caloric restriction lowers blood pressure. Environmental and dietary factors can influence the degree of hypertension
• Strain is significantly more sensitive to the hypotensive effects of GABA than normotensive Sprague-Dawley or WKY rats, with evidence that the effects are mediated by the brain angiotensin system.
• SHR rats express insulin resistance– Model, insulin resistance and essential
hypertension in non-obese humans• Have fewer glomeruli than WKY rats, but
they are of similar size, resulting in a reduced glomerular volume.– Consistent with the hypothesis that the kidney
plays an important role in hypertension • The strain is a suitable model for
screening anti-hypertensive drugs. • SHR rats are hyperactive and may be a
useful model for childhood hyperkinesis
SHR• SHR rats are hyperactive and
may be a useful model for childhood hyperkinesis and attention-deficit hyperactivity disorder
Biological Variability in Wistar-Kyoto RatsImplications for Research with the Spontaneously Hypertensive Rat
• SUMMARY The spontaneously hypertensive rat (SHR) initially bred in Kyoto is the most widely studied animal model of essential hypertension. As controls for the SHR, most workers have used normotensive descendants of Wistar rats from the colony in Kyoto from which the SHR strain was derived (Wistar-Kyoto rats, WKY). But the presumption that WKY are serviceable controls for SHR rests on the tacit assumption that all WKY constitute a single inbred strain. It appears, however, that whereas the National Institutes of Health distributed breeding stocks of SHR after they had been fully inbred (i.e., after 20 generations of brother-sister mating), the breeding stocks of WKY were distributed before they had been fully inbred. Accordingly, the biological variability of WKY may be greater than that of SHR. To investigate this possibility, we obtained SHR and WKY from two of the largest commercial suppliers in the United States and systematically measured the growth rate and blood pressure of these rats under identical physical and metabolic conditions. We found that WKY from one source differed from those of the other in both growth rate and blood pressure. In contrast, the SHR from the two suppliers were not different with respect to either growth rate or blood pressure. Because the National Institutes of Health may have distributed breeding stocks of WKY as early as the F6 generation, it is possible that rats currently designated as WKY do not constitute a single inbred strain. Thus, interpretation of studies employing "the Wistar-Kyoto rat strain" as a control for the SHR may be much more problematic than has previously been recognized.
Biological Variability in Wistar-Kyoto RatsImplications for Research with the Spontaneously Hypertensive Rat
• The spontaneously hypertensive rat (SHR) initially bred in Kyoto is the most widely studied animal model of essential hypertension.
• As controls for the SHR, most workers have used normotensive descendants of Wistar rats from the colony in Kyoto from which the SHR strain was derived (Wistar-Kyoto rats, WKY).
Biological Variability in Wistar-Kyoto RatsImplications for Research with the Spontaneously Hypertensive Rat
• But the presumption that WKY are serviceable controls for SHR rests on the tacit assumption that all WKY constitute a single inbred strain.
• It appears, however, that whereas the National Institutes of Health distributed breeding stocks of SHR after they had been fully inbred (i.e., after 20 generations of brother-sister mating), the breeding stocks of WKY were distributed before they had been fully inbred.
Biological Variability in Wistar-Kyoto RatsImplications for Research with the Spontaneously Hypertensive Rat
• Accordingly, the biological variability of WKY may be greater than that of SHR. To investigate this possibility, we obtained SHR and WKY from two of the largest commercial suppliers in the United States and systematically measured the growth rate and blood pressure of these rats under identical physical and metabolic conditions.
Biological Variability in Wistar-Kyoto RatsImplications for Research with the Spontaneously Hypertensive Rat
• We found that WKY from one source differed from those of the other in both growth rate and blood pressure. In contrast, the SHR from the two suppliers were not different with respect to either growth rate or blood pressure.
Biological Variability in Wistar-Kyoto RatsImplications for Research with the Spontaneously Hypertensive Rat
• Because the National Institutes of Health may have distributed breeding stocks of WKY as early as the F6 generation, it is possible that rats currently designated as WKY do not constitute a single inbred strain.
Biological Variability in Wistar-Kyoto RatsImplications for Research with the Spontaneously Hypertensive Rat
• Thus, interpretation of studies employing "the Wistar-Kyoto rat strain" as a control for the SHR may be much more problematic than has previously been recognized.
• FIOURE 1. Body weights of WKY from Taconic Farms (open symbols) and Charles River Laboratories (solid symbols) measured in three separate studies. Squares denote results of Study 1 (nine rats per vendor); triangles, Study 2 (seven rats per vendor); circles, Study 3 (nine rats per vendor). Symbols and their brackets indicate group means ± SE. In each study, analysis of covariance demonstrated that theslopes of the growth curves of the rats from the two vendors were significantly different.
• FIGURE 2. Body weights of SHR from Taconic Farms and Charles River Laboratories measured in three separate studies. Symbols and statistical analysis as in Figure 1. The slopes of the growth curves were not significantly different.
• FIGURE 3. Mean arterial pressures of unanesthetized, unrestrained WKY and SHR from Taconic Farms (open bars) and from Charles River Laboratories (solid bars). Blood pressures were measured at 20 weeks of age in nine WKY and nine SHR from each vendor. Vertical bars and their brackets indicate group means ± SE. The p value indicates a statistical difference between group means by Student's t test.
TABLE 1. Study-to-Study Variability of 10 Physiological orMetabolic Characteristics of SHR Relative to Those of WKY*
physiological characteristicHair colour white
life span 2.5‐3.5 years
Adult body weight
Male 300‐530g
Female 250‐300g
Body temperature 35.9‐37.5℃
Blood pressure
Male 18．7～20．0 kPa(140～150 mmHg)
Female 17．3 kPa(130 mmHg)
Respiratory rate 70‐115bpm
Heart rate 250‐450bpm
• Fig. 1: Blood pressure. In each subject, multiple tail cuff blood pressure measurements were performed over 3 days and averaged. The graph shows the average over the subjects, the error bar is SEM.
• Fig. 2: Body Weights. Body weights were measured two days before start of blood pressure measurements. Body weights did not change significantly during the course of the experiments.
• TABLE 1. Summary of Restriction Fragment Length Polymorphism Analysis and Estimation of Divergence Estimate
Application in biomedicine
• 1.Study on Hypertension
• 2.ADHD (Attention Deficit Hyperactivity Disorder) modol
• 3. Cerebral ischemia
• [10]). The various colonies of SHR are pre-hypertensive Health (USA) as an inbreed of the Wistar Kyoto colony via for the first 6–8 weeks of their lives with systolic blood brother3sister mating [10]. The degree of genetic differpressures around 100–120 mmHg [11], and then hyperten- ence between the SHR and WKY strains and within sion develops over the next 12–14 weeks [12]. As in different colonies of each strain is substantial and comparhumans, hypertension develops more rapidly and becomes able to the maximum divergence possible between unremore severe in male than female SHR [13]. In vivo studies lated humans [26,27] and thus unlikely to be related solely have shown that, in the early stages of hypertension, SHRs to hypertension. Differences between SHRs and Wistar have an increased cardiac output with normal total normotensive rats other than WKY may be more likely to peripheral resistance. As the SHR progresses into the be hypertension-related than differences between SHR and established hypertension state, the cardiac output returns to WKY because the SHRs were derived from the WKY, normal and the hypertrophied blood vessels produce an hypertension may develop spontaneously in the WKY, and increase in the total peripheral resistance [14]. the
• Systolic blood pressure (SBP) in (A) Sprague-Dawley (SD) rats treated with saline (group 1, n = 10, open circles) and adrenocorticotropic hormone (ACTH) (group 2, n = 10, closed circles); (B) Wistar rats treated with saline (group 3, n = 10, open squares) and ACTH (group 4, n = 10, closed squares); and body weight of (C) SD rats treated with saline (group 1, n = 10, open circles) and ACTH (group 2, n = 10, closed circles); (D) Wistar rats treated with saline (group 3, n = 10, open squares) and ACTH (group 4, n = 10, closed squares). T0 to T12 = treatment days
• Figure 1 Example of systolic blood pressure values on Friday (thick solid line) and during the weekend (an average of Saturday and Sunday, dotted line) from 10:00 until 16:00 h
6. Inbred Strains of Rats: SHRSP• 脑卒中易感性自发性高血压大鼠
6. Inbred Strains of Rats: SHRSP• Inbr. F59. Albino, c. • Origin: Substrains of SHR, further inbred with
selection of offspring of parents that died of stroke.
6. Inbred Strains of Rats: SHRSP• Inbr. F59. Albino, c. • Origin: Substrains of SHR, further inbred with
selection of offspring of parents that died of stroke.– Higher blood pressure (40-50 mmHg) than
SHR– Cerebral hemorrhage or infarction in 82% of
males over 100 days of age and 58% of females over 150 days of age.
6. Inbred Strains of Rats: SHRSP–Stroke is prevented by
antihypertensive agents–The incidence can be modified by diet,
being reduced , fish and vegetable oils.
–Excessive salt intake increases hypertension and its complications.
7. Inbred Strains of Rats: GK• Inbr. F40 (Galli et al, 1996). • Albino, c. • Origin: Developed from outbred Wistar
rats with selection for high glucose levels– Non-insulin dependent diabetes mellitus
(NIDDM)-related phenotypes• Fasting hyperglycemia• Impared secretion of insulin in response to glucose
both in vivo and in isolated pancreata• Hepatic and peripheral insulin resistance• Late complications: nephropathy, neuropathy
8. Zucker Rats
The obese condition appeared spontaneously in the 13 M strain when crossed to the Sherman strain. Dr.Theodore and Dr.Lois Zucker maintained the colony at the Laboratory of Comparative Pathology at Stow, MA, in 1961.In 1985, the Zucker maintained by Roche agency were imported to Charles River Laboratories Inc. ( USA ). In 1986, the uterine cesarean was implemented to make SPF colonies of Zucker.
Zucker rats are also called fa/fa rats. The obesity traits of the rats is inherited by autosomal recessivegenetic way, but the chromosomal
location is not clear.
Nomenclature:Crl:ZUC-Leprfa
Coat color • Predominantly brown• Brown and white dilute• Predominantly black• Black and white.
Anatomical characteristics• Lipid is not fully oxidized, and often
deposits in the heart , causing myocardial hypertrophy.
• The size of glomerulus increases.• Partial glomerular sclerosis.
Characteristics
• Feed more, present obesity.• Insulin resistance, hyperinsulinemia,
hypercholesterolemia. • Individuals maintaining the same of Leprfa
genetic factors present obesity.• From 4 weeks old, the obesity appearance
can be confirmed, weight increased sharply t i ll 10 weeks old.
• Blood sugar value is variable.• Infertility of homozygote.
Uses• Sugar, lipid metabolic abnormalities with
obesity.• Associated with obesity, the change of
adipose tissue, and related enzymes.• Insulin resistance. • Research related to renal function.
UsesZucker rats are a widely used as the
genetically obese disease model. The biggest value of Zucker rats is as the obesity model of human's proliferative hypertrophy obese disease.
Many scientists have used the model to study the onset, etiology, related pathology, possible treatment and various hypothetical mechanism of serious genetically obesity.
AT-LPL
UsesZucker rats are also used to study insulin
resistance. Zucker rats are good models to study insulin resistance.
Zucker rats are most widely used in the study of intervention of natural drug to insulin resistance.
UsesZucker rats can also be used as models of
noninsulin-dependent diabetes mellitus(NIDDM). But blood sugar of Zucker rats is relatively normal or occurs only mildhigh, so not so widely used.
The pathological characteristic of human NIDDM associated with obesity also exists in Zucker rats. But for high blood glucose levels and not resistant to glucose, they are
not the same.
