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.