Make a group and Make a mouse model!
Mouse model of drowsiness
Mouse model of alcohol intoxication
Different Anxiety level in inbred mice
Different level of Playfulness
C57BL/6J BALB/C
Mouse model of Playfulness
+/+ -/-
Mouse genetic approaches to behavior
Reverse Genetics & Forward Genetics
BMP7 knockout
Searching the geneFrom spontaneousmutants
Coisogenic & congenic
Coisogenic–If a mutation is induced in inbred mice–The new line is called by coisogenic
Congenic–Changing genetic background–e.g mice A with allele X (some phenotype) are crossed with inbred mice B–Among F1 mice obtained from A x B cross, mice with X allele crossed again with inbred B–By repeating this procedure, you can get congenic mice with X allele on genetic background of B
Nomenclature of inbred mice
C57BL/6J
C: Cold Spring Harbor laboratory 57: 57th femaleBL: black/6: 6th generationJ: Jackson laboratory
Nomenclature of Mutant Mice
C57BL/6J-a1atot
•C57BL/6J genetic background•a1a: alpha-1A calcium channel gene•Tot: tottering phenotype
129/sv-a1anull
•129/svgenetic background•a1a: alpha-1A calcium channel gene•Null: null mutation, Knockout
How to name a mutant allele
•Names based on primary features if the gene product of wild type allele
•Albino, himalayan, chinchilla (Tyrc, Tyrc-h, Tyrc-ch)
•Rules for deciding new gene names are made by a nomenclature committee (http://www.informatics.jax.org/mgihome/nomen/index.shtml)
•Many journals require that new allele names be approved by the nomenclature committee before publication
http://www.informatics.jax.org/mgihome/nomen/index.shtml
Laboratory Code
•J-The Jackson
•Mit-Laboratory Massachusetts Institute of Technology
•Leh-Hans Lehrach
•Kyo-Kyoto University
•Ztm-Central Animal Laboratory Medical School Hannover
•Unc-University of Northern California
How to name a gene
•Glra1:glycinereceptor, alpha 1
•Hk1-rs1 (ps1) :hexokinase-1 related sequence 1 (peudogene)
•KitW-v : Kitoncogeneallele name: viable dominant spotting
•Slc14a2_v1:solute carrier family 14, member 2, variant1
•Slc14a2_pr1 :solute carrier family 14, member 2, promoter1
•D8Mit17: the 17th locus mapped to mouse Chromosome 8 by M.I.T.
•Gt(ROSA)26Sor: the 26th gene "trapped" by the ROSA vector in the laboratory of Phillip Soriano (Sor)
•Ntn1Gt(pGT1.8TM)629Ska: the netrin1 (Ntn1) gene gene-trap allele
How to name transgene or targeted allele
Tg(CD8)1JwgA transgene containing the human CD8 gene, the first transgenic line using this construct described by the lab of Jon W. Gordon.
Car12Tn(sb-T2/GT2/tTA)1.1DlaGene Tn(transposon_class_abbreviation-vector)#Labcode
Cftrtm1UncThe first targeted mutation(tm) of the cystic fibrosis transmembraneregulator (Cftr) gene produced at the University of North Carolina.
Explain following words each other
•Co-isogenicmice
•Congenicmice
•Outbredmice
•F1 mice
•Inbred mice
The most efficient way for robust outputs in behavioral studies
ES Cells into
Blastocysts
Strain with recessive coat color
neo
neo
ES Cell
Transfection
of targeting
vector
Germ-line
Germ-line
F1
Chimera
Embryo
Transfer
to Uterus
Foster
F2
X X
X
Cosiogenic B6(N1)
B6(N6~20)
X
-/- +/+
F1 wild & mutant
Chimera129 B6
B6 Congenic
X
F1 X
+/+ -/-
F2
Chimera