Hybrid male sterility (HMS) contributes to reproductive isolation commonly observed among house mouse (Mus musculus) subspecies, both in the wild and in laboratory crosses. Incompatibilities involving specific Prdm9 alleles and certain Chromosome (Chr) X genotypes are known determinants of fertility and HMS, and previous work in the field has demonstrated that genetic background modifies these two major loci. We constructed hybrids that have identical genotypes at Prdm9 and identical X chromosomes, but differ widely across the rest of the genome. In each case, we crossed female PWK/PhJ mice representative of the M. m. musculus subspecies to males from a classical inbred strain representative of M. m. domesticus: 129S1/SvImJ, A/J, C57BL/6J, or DBA/2J. We detected three distinct trajectories of fertility among the hybrids using breeding experiments. The PWK129S1 males were always infertile. PWKDBA2 males were fertile, despite their genotypes at the major HMS loci. We also observed age-dependent changes in fertility parameters across multiple genetic backgrounds. The PWKB6 and PWKAJ males were always infertile before 12 weeks and after 35 weeks. However, some PWKB6 and PWKAJ males were transiently fertile between 12 and 35 weeks. This observation could resolve previous contradictory reports about the fertility of PWKB6. Taken together, these results point to multiple segregating HMS modifier alleles, some of which have age-related modes of action. The ultimate identification of these alleles and their age-related mechanisms will advance understanding both of the genetic architecture of HMS and of how reproductive barriers are maintained between house mouse subspecies.

中文翻译：

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年龄和遗传背景改变了家鼠的杂交雄性不育性。


杂交雄性不育（HMS）有助于家鼠（ Mus musculus ）亚种中常见的生殖隔离，无论是在野外还是在实验室杂交中。涉及特定Prdm9等位基因和某些染色体 (Chr) X 基因型的不相容性是生育力和 HMS 的已知决定因素，该领域之前的工作已经证明遗传背景会改变这两个主要基因座。我们构建了在Prdm9处具有相同基因型和相同 X 染色体的杂交体，但在基因组的其余部分有很大差异。在每种情况下，我们都将代表M. m.的雌性 PWK/PhJ 小鼠进行杂交。 musculus亚种到雄性，来自代表M. m.的经典近交系。国内：129S1/SvImJ、A/J、C57BL/6J 或 DBA/2J。我们通过育种实验检测到杂交种之间三种不同的生育轨迹。 PWK129S1 雄性始终不育。尽管 PWKDBA2 雄性在主要 HMS 基因座上有基因型，但它们具有生育能力。我们还观察到多种遗传背景下生育参数随年龄的变化。 PWKB6和PWKAJ雄性在12周前和35周后始终不育。然而，一些 PWKB6 和 PWKAJ 雄性在 12 至 35 周之间短暂具有生育能力。这一观察结果可以解决之前关于 PWKB6 生育力的相互矛盾的报告。总而言之，这些结果表明存在多个分离的 HMS 修饰等位基因，其中一些具有与年龄相关的作用模式。这些等位基因及其年龄相关机制的最终鉴定将促进对 HMS 遗传结构以及家鼠亚种之间生殖障碍如何维持的理解。