Research press release





今回Kimberly Cooperたちは、雌の実験用マウスに用いる遺伝子ドライブ系の開発に成功した。Cooperたちは、CRISPR-Cas9法を用いて、配偶子形成と胚発生のさまざまな段階でゲノム編集を行って遺伝子伝播の最適化を図り、チロシナーゼ(Tyr)遺伝子の特定の改変対立遺伝子がマウスの親から子へ継承される確率を高めた。この遺伝子ドライブ系は、雄の生殖系列ではうまくいかなかったが、雌の生殖系列を標的とした場合には、Tyr遺伝子の対立遺伝子の継承率を上昇させた。Cooperたちは、今回の研究で検証された遺伝子ドライブ系のうち最も効率の高いものであれば、必要な単一の対立遺伝子の継承率を平均で50%から約70%に上昇させることができると報告している。


The feasibility of gene drives, a strategy to increase the inheritance of specific gene variants (alleles) within a population, is demonstrated in lab mice, reports a paper published online this week in Nature. Although further work is required before gene drives can be used in strategies to control wild mouse populations, these results could aid the development of improved mouse models for research into complex genetic diseases.

Gene drives bias the transmission of particular alleles so that they are inherited more often than by random chance - so-called ‘Super-Mendelian’ inheritance. Efficient gene drives have recently been developed in insects (to reduce certain mosquito populations, for example), but such systems have yet to be successfully developed in mammals owing to differences in genetic inheritance mechanisms.

Kimberly Cooper and colleagues developed a successful gene drive system in female laboratory mice. The authors used CRISPR-Cas9 genome editing to increase the odds that mouse offspring would inherit a specific engineered allele of the tyrosinase gene (Tyr) from their parents, by timing the editing to different stages of gamete production and embryonic development to optimize gene transmission. Although the strategy was not successful in the male germline, when the female germline was targeted the rate of inheritance of the Tyr allele increased. The authors report that the most efficient of the strategies they tested would, on average, increase the inheritance of a single desired allele from 50% to about 70%.

The authors conclude that further work is needed to increase the frequency of gene inheritance in the offspring of both male and female mice, but that the efficiency achieved here is sufficient for a broad range of laboratory applications.

doi: 10.1038/s41586-019-0875-2

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