CRISPR/Cas9-mediated mosaic mutation of SRY gene induces hermaphroditism in rabbits

Hermaphroditism is a rare disorder that affects sexual development, resulting in individuals with both male and female sexual organs. Hermaphroditism is caused by anomalies in genes regulating sex determination, gonad development, or expression of hormones and their receptors during embryonic development during sexual differentiation. SRY is a sex-determination gene on the Y chromosome that is responsible for initiating male sex determination in mammals. In this study, we introduced CRISPR/Cas9-mediated mutations in the high-mobility-group (HMG) region of the rabbit SRY. As expected, SRY-mutant chimeric rabbits were diagnosed with hermaphroditism, characterized by possessing ovotestis, testis, ovary and uterus simultaneously. Histopathology analysis revealed that the testicular tissue was immature and lacked spermatogenic cells, while the ovarian portion appeared normal and displayed follicles at different stages. This is the first report of a rabbit hermaphroditism model generated by the CRISPR/Cas9 system. This novel rabbit model could advance our understanding of the pathogenesis of hermaphroditism, and identify novel therapies for human clinical treatment of hermaphroditism.