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首页> 外文期刊>Scientific reports. >CRISPR/Cas9-mediated genome editing in wild-derived mice: generation of tamed wild-derived strains by mutation of the a (nonagouti) gene
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CRISPR/Cas9-mediated genome editing in wild-derived mice: generation of tamed wild-derived strains by mutation of the a (nonagouti) gene

机译：CRISPR / CAS9介导的野生小鼠中的基因组编辑：通过A（非诱导）基因的突变产生驯化的野生衍生菌株的产生

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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.
机译：狂野衍生的小鼠通过其遗传多样性导致实验小鼠遗传学，这可能有助于增加识别负责特定表型和疾病的新型改性基因的机会。然而，由于稳定​​的胚胎干细胞的不可用性，使用野生衍生的小鼠靶向的基因已经不成功。在这里，我们认为CRISPR / CAS9介导的基因靶向可以应用于日本野生衍生的MSM / MS菌株（Mus Musculus molossinus）。我们瞄准编码在头发和大脑中局部化的agouti蛋白的非引发剂（a）基因。我们获得了三只纯合的敲除为创始人，所有人都显示了黑色涂层颜色。虽然纯合的敲除后代在生理学上与野生型垃圾伴侣无法区分，但它们显示出特定的驯化行为：在黑暗阶段的下降性和避免人类手中的下降。这些表型在随后的几代中一致。我们的调查结果支持实证假设，即非代购是一种驯化链接基因，其损失可能会压抑攻击行为。

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