Human Globozoospermia-Related Gene Spata16 Is Required for Sperm Formation Revealed by CRISPR/Cas9-Mediated Mouse Models.

Abstract

A recent genetic analysis of infertile globozoospermic patients identified causative mutations in three genes: a protein interacting with C kinase 1 (), dpy 19-like 2 (), and spermatogenesis associated 16 (). Although mouse models have clarified the physiological functions ofandduring spermatogenesis,remains to be determined. Globozoospermic patients carried a homozygous point mutation inat 848G→A/R283Q. We generated CRISPR/Cas9-mediated mutant mice with the same amino acid substitution in the fourth exon ofto analyze the mutation site at R284Q, which corresponded with R283Q of mutated human SPATA16. We found that the point mutation inwas not essential for male fertility; however, deletion of the fourth exon ofresulted in infertile male mice due to spermiogenic arrest but not globozoospermia. This study demonstrates thatis indispensable for male fertility in mice, as well as in humans, as revealed by CRISPR/Cas9-mediated mouse models.