Normal Fertility of Dnajb13 (exon2 KO)/(exon2 c.106T > C Mut) Compound Heterozygous Mutant Male Mice.

Asthenozoospermia is a common factor in male infertility, and male infertility associated with primary ciliary dyskinesia (PCD) is usually caused by asthenozoospermia. Previously, we identified a heterozygous mutation DNAJB13 c.106T > C (p.Ser36Pro) in 9 patients with idiopathic oligozoospermia. Carriers exhibit reduced sperm motility, decreased DNAJB13 protein levels, abnormal localization of DNAJB13 protein in sperm, and male infertility. To investigate the mechanistic role of this mutation, we generated a Dnajb13 compound heterozygous mouse model (exon2 KO/exon2 c.106T > C Mut). Contrary to human phenotypes, Dnajb13 c.106T > C heterozygous mice showed no significant defects in spermatogenesis or fertility. These results indicate a species-specific discrepancy in the phenotypic expression of this missense mutation. We therefore propose that the DNAJB13 c.106T > C variant should be classified as a “variant of uncertain significance”.