A New Model for Elucidating the Genetic Mechanisms of Hybrid Male Sterility in House Mice

阐明家鼠杂交雄性不育遗传机制的新模型

• 批准号: 10592916
• 负责人: David Lawrence Aylor
• 金额: $ 22.8万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-23 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10592916
• 关键词: Affect; Alleles; Animals; Biological; Cells; Data; European; Exhibits; Female; Fertility; Future; Generations; Genes; Genetic; Genetic Polymorphism; Genetic Recombination; Genetic Variation; Genetic study; Genomics; Genotype; Germ Cells; Goals; House mice; Human; Human Biology; Hybrids; Impairment; Inbred Strain; Inbred Strains Mice; Infertility; Male Infertility; Male Sterility; Maps; Meiosis; Microtus; Modeling; Molecular; Mouse Strains; Mus; Nature; Partner in relationship; Phenotype; Play; Population; Process; Quantitative Trait Loci; Reproductive Biology; Research; Research Project Grants; Resolution; Resources; Role; Spermatogenesis; Spermatogenic Cell; Sterility; Synaptonemal Complex; Variant; X Chromosome; cell type; design; experimental study; genetic architecture; genetic variant; male; novel; offspring; prevent; public health relevance; reproductive; trait; transcriptome sequencing

PROJECT SUMMARY A major goal in evolutionary genetics is to identify the genetic variants that give rise to hybrid sterility, and to understand their mechanisms of action. Hybrid sterility is important because it maintains barriers between species in nature. The house mouse, Mus musculus, presents a unique opportunity to study the genetics of hybrid sterility due to the substantial but incomplete reproductive isolation between two subspecies (M.m.musculus and M.m.domesticus). Male offspring born to a musculus female and a domesticus male often exhibit hybrid male sterility (HMS). This phenomenon can be replicated experimentally using inbred mouse strains that are representative of each subspecies. Two major genetic factors have been shown to cause HMS, but many of the genes involved remain unknown. We recently identified a specific type of hybrid male that has the known HMS-associated QTL genotypes, yet is fertile and shows no reproductive impairment. The goals of this exploratory research project are to identify the genetic variants that rescue fertility in this hybrid, to identify the stage of spermatogenesis affected by those variants, and to identify the molecular differences between infertile and fertile hybrid males. These results will advance our understanding of evolutionary genetics, reproductive biology, and meiosis.

项目总结 进化遗传学的一个主要目标是识别导致杂交不育的遗传变异， 并了解它们的作用机制。杂交不育很重要，因为它存在障碍 在自然界中的物种之间。家鼠，Mus Musculus，提供了一个独特的研究机会 杂种不育的遗传学是由于它们之间大量但不完全的生殖隔离 亚种(M.m.Musculus和M.m.home ticus)。雌性肌肉所生的雄性后代和 家蝇雄性常表现出杂种雄性不育(HMS)。这种现象是可以复制的 实验使用代表每个亚种的近亲交配的小鼠品系。 有两个主要的遗传因素被证明是导致HMS的原因，但其中的许多基因仍然存在 未知。我们最近发现了一种特定类型的杂交雄性，它具有已知的与HMS相关的QTL 但仍有生育能力，没有表现出生殖障碍。这项探索性研究的目标是 该项目的目的是确定挽救杂交后代生育能力的遗传变异，以确定 这些变异对精子发生的影响，并鉴定不育之间的分子差异 和有生育能力的混血雄性。这些结果将促进我们对进化遗传学的理解， 生殖生物学和减数分裂。