Establishment and Analysis of Actin-like 7b deficient mice – a tool to study male factor infertility.

• Applicant: Professor Dr. Hubert Schorle
• Subject Area: Reproductive Medicine, Urology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 508975304

Defects during gamete formation may impede successful fertilization, resulting in infertility. Infertility is clinically defined as “a disease of the reproductive system defined by the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse. Multiple factors have been described to cause male infertility including genetic aberrations as well as environmental influences. Still, in 37-58% of cases the exact cause for male infertility remains unknown. To develop potential treatment strategies for male infertility or predict the success when applying Artificial Reproduction Technologies (ART), it is necessary to get a detailed understanding of the genes and pathways involved in male gamete formation. Among others, the actin-like protein 7b (ACTL7b) is described to be specifically expressed in testes in round and elongated spermatids only. Interestingly in a cohort of Japanese infertile male patients, 4 polymorphisms in ACTL7b were detected, suggesting a potential role of ACTL7b in fertility. Further, ACTL7b was detected in a screen for genes important for spermatogenesis in swamp buffalo and seems to be involved in controlling litter size in mutton. We have deleted the Actl7b gene using CRISPR-Cas9 mediated gene editing in zygotes. Preliminary results support the hypothesis of ACTL7b being required for spermatogenesis. Male animals deficient for Actl7b are infertile and show a developmental arrest during spermiogenesis. In order to fully understand the phenotype observed, we propose now a detailed analysis of the ACTL7b deficient mice using classical histology, immunohistochemistry, Mass. Spec and CoIP analyses. With this we are able to precisely describe the function and role of ACTL7b in the context of spermiogenesis in particular and male factor infertility in general.

• DFG Programme: Research Grants