title: CRISPR/Cas9-mediated genome editing in wild-derived mice: generation of tamed wild-derived strains by mutation of the a (nonagouti) gene.
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.
authors.affiliation: RIKEN BioResource Center, Tsukuba, Ibaraki 305-0074, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Hirose
authors.affiliation: RIKEN BioResource Center, Tsukuba, Ibaraki 305-0074, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Hasegawa
authors.affiliation: RIKEN BioResource Center, Tsukuba, Ibaraki 305-0074, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Mochida
authors.affiliation: RIKEN BioResource Center, Tsukuba, Ibaraki 305-0074, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Matoba
authors.affiliation: RIKEN BioResource Center, Tsukuba, Ibaraki 305-0074, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hatanaka
authors.affiliation: RIKEN BioResource Center, Tsukuba, Ibaraki 305-0074, Japan.|Graduate School of Life and Environmental Science, University of Tsukuba, Ibaraki 305-8572, Japan.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Inoue
authors.affiliation: Department of Biological Production Science, College of Agriculture, Ibaraki University, Ami, Ibaraki 300-0393, Japan.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Goto
authors.affiliation: RIKEN BioResource Center, Tsukuba, Ibaraki 305-0074, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Kaneda
authors.affiliation: RIKEN BioResource Center, Tsukuba, Ibaraki 305-0074, Japan.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Yamada
authors.affiliation: RIKEN BioResource Center, Tsukuba, Ibaraki 305-0074, Japan.
authors.forename: Tamio
authors.initials: T
authors.lastname: Furuse
authors.affiliation: RIKEN BioResource Center, Tsukuba, Ibaraki 305-0074, Japan.
authors.forename: Kuniya
authors.initials: K
authors.lastname: Abe
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi 464-8601, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Uenoyama
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi 464-8601, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tsukamura
authors.affiliation: RIKEN BioResource Center, Tsukuba, Ibaraki 305-0074, Japan.
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Wakana
authors.affiliation: RIKEN BioResource Center, Tsukuba, Ibaraki 305-0074, Japan.|Organization for Promotion of Tenure Track, University of Miyazaki, Miyazaki 889-1692, Japan.
authors.forename: Arata
authors.initials: A
authors.lastname: Honda
authors.affiliation: RIKEN BioResource Center, Tsukuba, Ibaraki 305-0074, Japan.|Graduate School of Life and Environmental Science, University of Tsukuba, Ibaraki 305-8572, Japan.|The Center for Disease Biology and Integrative Medicine, Faculty of Medicine, University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Atsuo
authors.initials: A
authors.lastname: Ogura
mesh_terms: D054366:Agouti Signaling Protein / Q000235:genetics; D000483:Alleles; D000818:Animals; D000835:Animals, Wild; D064113:CRISPR-Cas Systems; D004252:DNA Mutational Analysis; D004298:Dopamine / Q000378:metabolism; D000072669:Gene Editing; D015870:Gene Expression; D006801:Humans; D008636:Mesencephalon / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D010641:Phenotype
chemical_list: D054366:Agouti Signaling Protein; C515183:a protein, mouse; D004298:Dopamine