Project 1 - Genetics of male infertility in the Collaborative Cross resource

PROJECT SUMMARY: Project 1 The Collaborative Cross (CC) is a popular system genetics platform to study biomedical traits and as a rich source of optimized models of human disease. The CC is an integral part of the MMRRC at UNC and represents over 85% of live mice distributed by our center. During the inbreeding phase of the CC project, 95% of the CC lines became extinct in large part due to male infertility. Even after the major wave of extinction, the extant CC lines remain a challenging population to breed. Since 2019 the continued success of the CC as a platform has been predicated on maintaining a stable set of 63 CC strains readily available for the community. In other words, strains that are most challenging to breed and are also the most expensive to maintain live in the shelf, are critical for the project. A subset of the most challenging strains are characterized by high incidence of male infertility, with incidence approaching 50% in the following four CC strains: CC031/GeniUnc, CC065/Unc, CC072/TauUnc and CC075/Unc. Here we propose to use genetic analysis to identify, and eliminate or reduce the impact of male infertility in the four CC strains with the highest incidence of male infertility.