make a group and make a mouse model! - kaistbs.kaist.ac.kr/~brain/lecture/2010spring/case...
TRANSCRIPT
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Make a group and Make a mouse model!
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Mouse model of drowsiness
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Mouse model of alcohol intoxication
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Different Anxiety level in inbred mice
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Different level of Playfulness
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C57BL/6J BALB/C
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Mouse model of Playfulness
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+/+ -/-
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Mouse genetic approaches to behavior
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Reverse Genetics & Forward Genetics
BMP7 knockout
Searching the geneFrom spontaneousmutants
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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
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Nomenclature of inbred mice
C57BL/6J
C: Cold Spring Harbor laboratory 57: 57th femaleBL: black/6: 6th generationJ: Jackson laboratory
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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
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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
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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
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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
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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.
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Explain following words each other
•Co-isogenicmice
•Congenicmice
•Outbredmice
•F1 mice
•Inbred mice
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The most efficient way for robust outputs in behavioral studies
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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
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X X
X
Cosiogenic B6(N1)
B6(N6~20)
X
-/- +/+
F1 wild & mutant
Chimera129 B6
B6 Congenic
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X
F1 X
+/+ -/-
F2
Chimera