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.

项目概要 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，因为它保持了障碍 自然界中的物种之间。家鼠（Mus musculus）提供了独特的研究机会 由于两个品种之间存在实质性但不完全的生殖隔离而导致杂交不育的遗传学 亚种（M.m.musculus 和 M.m.domesticus）。肌肉发达的女性和肌肉发达的女性所生的男性后代 家蝇雄性经常表现出杂种雄性不育（HMS）。这种现象是可以复制的 使用代表每个亚种的近交系小鼠品系进行实验。 两个主要的遗传因素已被证明会导致 HMS，但许多相关基因仍然存在 未知。我们最近鉴定了一种特定类型的杂交雄性，其具有已知的 HMS 相关 QTL 基因型，但具有生育能力并且没有表现出生殖障碍。这项探索性研究的目标 该项目的目的是识别挽救这种杂交后代生育能力的遗传变异，以确定其所处的阶段 受这些变异影响的精子发生，并鉴定不育症之间的分子差异 和可育的杂交雄性。这些结果将增进我们对进化遗传学的理解， 生殖生物学和减数分裂。