Actl7b-deficiency leads to mislocalization of LC8 type dynein light chains and disruption of murine spermatogenesis.

Actin-related proteins (Arp) are classified according to their similarity to actin and are involved in diverse cellular processes. ACTL7B is a testis-specific Arp and highly conserved in rodents and primates. ACTL7B is specifically expressed in round and elongating spermatids during spermiogenesis. Here, we have generated an Actl7b-null allele in mice to unravel the role of ACTL7B in sperm formation. Male mice homozygous for the Actl7b-null allele (Actl7b-/-) were infertile, while heterozygous males (Actl7b+/-) were fertile. Severe spermatid defects such as detached acrosomes, disrupted membranes and flagella malformations start to appear after spermiogenesis step 9 in Actl7b-/- mice, finally resulting in spermatogenic arrest. Abnormal spermatids were degraded and autophagy markers were increased. Co-immunoprecipitation with MassSpec experiments identified interaction between ACTL7B and the LC8 dynein light chains DYNLL1 and DYNLL2, which are first detected in step 9 spermatids and mislocalized when ACTL7B is absent. Our data unequivocally establishes that mutations in ACTL7B are directly related to male infertility, pressing for additional research in men.