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 failed elongation of the axoneme start to appear at spermiogenesis step 9 in Actl7b-/- mice, finally resulting in spermatogenic arrest. Abnormal spermatids, were degraded. Co-immunoprecipitation 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. Summary statement In this study, Actl7b-deficient mice were generated. Loss of Actl7b leads to spermatogenic arrest in mice. ACTL7B interacts in with DYNLL1/DYNLL2 and seems to function in spermatid cytoskeleton.