Abstract
Cep215/Cdk5rap2 is a centrosome protein crucial for directing microtubule organization during cell division and morphology. Cep215 is a causal gene of autosomal recessive primary microcephaly type 3, characterized by a small brain size and a thin cerebral cortex. Despite previous attempts with Cep215 knockout (KO) mice to elucidate its developmental roles, interpreting their phenotypes remained challenging due to potential interference from alternative variants. Here, we generated KO mice completely lacking the Cep215 gene and investigated its specific contributions to male germ cell development. In the absence of Cep215, testis size decreased significantly, accompanied by a reduction in male germ cell numbers. Histological analyses unveiled the arrested development of male germ cells around the zygotene stage of meiosis. Concurrently, the formation of the blood-testis barrier (BTB) was impaired in Cep215 KO testes. These findings suggest that BTB failure contributes, at least partially, to male germ cell defects observed in Cep215 KO mice. We propose that the deletion of Cep215 may disrupt microtubule organization in Sertoli cells with a delay in spermatogonial stem cell mitosis, thereby impeding proper BTB formation.