不尽相同的性染色体和常染色体配对、联会和重组是哺乳动物精子发生减数分裂的典型特征和核心事件，但其调控机制不清楚。我们假设：减数分裂DNA双链断裂的同源修复中单链DNA上RAD51募集机制的不同决定了哺乳动物精子发生中性染色体和常染色体减数分裂行为的差异。本项目将利用我们建立的也是迄今已知唯一的仅表现为性染色体假常染色体区（PAR）和可能只表现为常染色体上RAD51募集缺陷的动物模型Rad51ap2和Tex15敲除小鼠，结合CRISPR/Cas9等技术，研究揭示RAD51AP2为什么只调节及如何调节精子发生性染色体PAR区RAD51的招募，探讨TEX15是否以及为何只调节和如何调节常染色体上RAD51的募集，以期揭示哺乳动物精子发生中性染色体和常染色体减数分裂行为及其差异的调控机制，提出减数分裂染色体行为调控的新理论，为减数分裂异常所致精子发生异常相关疾病的病理机制阐释和诊治，提供新思维。

The pairing, synapsis and recombination between homologous chromosomes and their dimorphism between sex chromosomes and autosomes are typical features and core events of meiosis during spermatogenesis in mammals. However, the molecular mechanisms that underlie and coordinate these events remain poorly understood. Here, we propose that the difference in RAD51 recruitment during homologous repair after formation of programmed double-stranded DNA breaks (DSBs) is one of the main causes for dimorphism of the chromosome behavior between the sex chromosomes and autosomes. In this project, we will use the two animal models that are generated by ourselves, Rad51ap2 (RAD51-associated protein 2) KO mice, which are the only known mouse model with defects in RAD51 recruitment on pseudoautosomal region (PAR) of the sex chromosomes only, as well as Tex15 (Testis-expressed sequence 15 protein) KO mice, which may be the only mouse model with defects in RAD51 recruitment only on autosomes till now. Combined with the advanced techniques including CRISPR/Cas9 gene editing, we will explore why and how RAD51AP2 only regulates recruitment of RAD51 on PAR. We will determine experimentally whether TEX15 only regulates recruitment of RAD51 on autosomes. If it indeed regulates the recruitment of RAD51 on autosomes only, we will study why and how TEX15 works. This project will hopefully uncover molecular mechanisms underlying the behaviors of meiotic chromosomes, and their dimorphism between the sex chromosomes and autosomes, and propose new models for the regulation and coordination of the chromosome behaviors during male meiosis in mammals. Our findings are also expected to provide new insights into the causes, diagnosis and treatment of infertility, spontaneous abortions and birth defects induced by meiotic abnormalities in human males.