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Leveraging a natural murine meiotic drive to suppress invasive populations.

Luke GierusAysegul BirandMark D BuntingGelshan I GodahewaSandra G PiltzKevin P OhAntoinette J PiaggioDavid W ThreadgillJohn R GodwinOwain EdwardsPhillip CasseyJoshua V RossThomas A A ProwsePaul Q Thomas
Published in: Proceedings of the National Academy of Sciences of the United States of America (2022)
Invasive rodents are a major cause of environmental damage and biodiversity loss, particularly on islands. Unlike insects, genetic biocontrol strategies including population-suppressing gene drives with biased inheritance have not been developed in mice. Here, we demonstrate a gene drive strategy (<i>t</i><sub>CRISPR</sub>) that leverages super-Mendelian transmission of the <i>t</i> haplotype to spread inactivating mutations in a haplosufficient female fertility gene (<i>Prl</i>). Using spatially explicit individual-based in silico modeling, we show that <i>t</i><sub>CRISPR</sub> can eradicate island populations under a range of realistic field-based parameter values. We also engineer transgenic <i>t</i><sub>CRISPR</sub> mice that, crucially, exhibit biased transmission of the modified <i>t</i> haplotype and <i>Prl</i> mutations at levels our modeling predicts would be sufficient for eradication. This is an example of a feasible gene drive system for invasive alien rodent population control.
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