Heterozygous mutation in BRCA2 induces accelerated age-dependent decline in sperm quality with male subfertility in rats.

ABSTRACT: Tumor suppressor BRCA2 executes homologous recombination to repair DNA double-strand breaks in collaboration with RAD51, involving exon 11 and 27. Exon 11 constitutes a region where pathogenic variants (PVs) accumulate, and mutations in this region are known to contribute to carcinogenesis. However, the impact of the heterozygous PVs of BRCA2 exon 11 on the life quality beyond cancer risk, including male fertility, remains unclear. Here, we established a rat model with a frameshift on the seventh BRC repeat in Brca2 exon 11 (Brca2^+/p.T1942fs), which is homologous to human BRCA2^+/p.T1974fs, using CRISPR/Cas9 system. Our analyses revealed that the heterozygous rats with the PV in the BRCA2 exon 11 showed increased DNA double-strand breaks and apoptosis in spermatogonia

SUBMITTER: Motooka Y 

PROVIDER: S-EPMC11696240 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature