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

肌动蛋白样 7b 缺陷小鼠的建立和分析——研究男性因素不育的工具。

• 批准号: 508975304
• 负责人: Professor Dr. Hubert Schorle
• 金额: --
• 依托单位: Institut für Pathologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/508975304?language=en
• 关键词: Establishment; Analysis; Actin; like; 7b

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.

配子形成过程中的缺陷可能会阻碍成功受精，导致不孕不育在临床上被定义为“一种生殖系统疾病，其定义为在 12 个月或更长时间的定期无保护性交后未能实现临床妊娠。”导致男性不育的原因包括遗传畸变以及环境影响，但在 37-58% 的病例中，男性不育的确切原因仍不清楚。为了制定男性不育策略或预测应用人工生殖技术 (ART) 的成功，有必要详细了解参与雄性配子形成的基因和途径，其中描述了肌动蛋白样蛋白 7b (ACTL7b)。仅在一组日本不育男性患者中暗示在睾丸中的圆形和细长精子细胞中特异表达，检测到 ACTL7b 的 4 个多态性，表明 ACTL7b 在此外，在对沼泽水牛精子发生重要基因的筛选中检测到了 ACTL7b，该基因似乎参与了羊肉产仔数的控制，初步结果支持了这一观点。精子发生需要 ACTL7b 的假设。缺乏 Actl7b 的雄性动物不育，并且在精子发生过程中表现出发育停滞。观察到，我们现在建议使用经典组织学、免疫组织化学、质谱和 CoIP 分析对 ACTL7b 缺陷小鼠进行详细分析，这样我们就能够精确描述 ACTL7b 在精子发生（特别是男性因素）中的功能和作用。一般不孕症。