RRC ID 47687
Author Hirose M, Hasegawa A, Mochida K, Matoba S, Hatanaka Y, Inoue K, Goto T, Kaneda H, Yamada I, Furuse T, Abe K, Uenoyama Y, Tsukamura H, Wakana S, Honda A, Ogura A.
Title CRISPR/Cas9-mediated genome editing in wild-derived mice: generation of tamed wild-derived strains by mutation of the a (nonagouti) gene.
Journal Sci Rep
Abstract Wild-derived mice have contributed to experimental mouse genetics by virtue of their genetic diversity, which may help increase the chance of identifying novel modifier genes responsible for specific phenotypes and diseases. However, gene targeting using wild-derived mice has been unsuccessful because of the unavailability of stable embryonic stem cells. Here, we report that CRISPR/Cas9-mediated gene targeting can be applied to the Japanese wild-derived MSM/Ms strain (Mus musculus molossinus). We targeted the nonagouti (a) gene encoding the agouti protein that is localized in hair and the brain. We obtained three homozygous knockout mice as founders, all showing black coat colour. While homozygous knockout offspring were physiologically indistinguishable from wild-type litter-mates, they showed specific domesticated behaviours: hypoactivity in the dark phase and a decline in the avoidance of a human hand. These phenotypes were consistent over subsequent generations. Our findings support the empirical hypothesis that nonagouti is a domestication-linked gene, the loss of which might repress aggressive behaviour.
Volume 7
Pages 42476
Published 2017-2-14
DOI 10.1038/srep42476
PII srep42476
PMID 28195201
PMC PMC5307340
MeSH Agouti Signaling Protein / genetics Alleles Animals Animals, Wild CRISPR-Cas Systems* DNA Mutational Analysis Dopamine / metabolism Gene Editing* Gene Expression Humans Mesencephalon / metabolism Mice Mice, Knockout Mutation Phenotype
IF 3.998
Times Cited 3
Mice RBRC00209