Human Globozoospermia-Related Gene Spata16 Is Required for Sperm Formation Revealed by CRISPR/Cas9-Mediated Mouse Models.
A recent genetic analysis of infertile globozoospermic patients identified causative mutations in three genes: a protein interacting with C kinase 1 (PICK1), dpy 19-like 2 (DPY19L2), and spermatogenesis associated 16 (SPATA16). Although mouse models have clarified the physiological functions of Pick1 and Dpy19l2 during spermatogenesis, Spata16 remains to be determined. Globozoospermic patients carried a homozygous point mutation in SPATA16 at 848G→A/R283Q. We generated CRISPR/Cas9-mediated mutant mice with the same amino acid substitution in the fourth exon of Spata16 to analyze the mutation site at R284Q, which corresponded with R283Q of mutated human SPATA16. We found that the point mutation in Spata16 was not essential for male fertility; however, deletion of the fourth exon of Spata16 resulted in infertile male mice due to spermiogenic arrest but not globozoospermia. This study demonstrates that Spata16 is indispensable for male fertility in mice, as well as in humans, as revealed by CRISPR/Cas9-mediated mouse models.
['Fujihara|Yoshitaka|Y|', 'Oji|Asami|A|', 'Larasati|Tamara|T|', 'Kojima-Kita|Kanako|K|', 'Ikawa|Masahito|M|0000-0001-9859-6217']
D000818:Animals D001483:Base Sequence D064113:CRISPR-Cas Systems D004195:Disease Models, Animal D005091:Exons D000072669:Gene Editing D018398:Homeodomain Proteins D006720:Homozygote D007248:Infertility, Male D008297:Male D051379:Mice D008822:Mice, Transgenic D017354:Point Mutation D017384:Sequence Deletion D000072660:Teratozoospermia D033921:Vesicular Transport Proteins
mouse model spermatogenesis point mutation genome editing male infertility testis