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.

项目摘要 进化遗传学的一个主要目标是识别引起杂种不育的遗传变异， 并了解它们的作用机制。杂种不育性很重要，因为它保持了 自然界中的物种之间。家鼠，小家鼠，提供了一个研究 杂种不育的遗传学是由于两个品种之间实质上但不完全的生殖隔离造成的， 亚种（M.m.musculus和M.m. musculicus）。雄性后代出生的小肌肉女性和一个 雄性不育系常表现为杂种雄性不育（HMS）。这种现象可以复制 实验上使用代表每个亚种的近交系小鼠品系。 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。 未知我们最近发现了一种特定类型的杂交雄性，具有已知的HMS相关QTL 基因型，但能生育，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拯救这种杂交后代生育能力的遗传变异，以确定 精子发生受这些变异体的影响，并确定不育之间的分子差异 和能生育的杂交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。