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