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阻碍成功受精，导致不育。不孕症在临床上被定义为“一种生殖系统疾病，其特征是在12个月或更长时间的无保护的常规性交后未能实现临床妊娠。”多种因素已被描述为导致男性不育，包括遗传畸变和环境影响。然而，在37-58%的病例中，男性不育的确切原因尚不清楚。为了制定男性不育的潜在治疗策略或预测应用人工生殖技术（ART）的成功与否，有必要详细了解男性配子形成的基因和途径。其中，肌动蛋白样蛋白7b （ACTL7b）被描述为仅在睾丸中圆形和细长精子中特异性表达。有趣的是，在一组日本男性不育患者中，检测到4个ACTL7b多态性，表明ACTL7b在生育中可能起作用。此外，ACTL7b在沼泽水牛精子发生的重要基因筛选中被检测到，似乎与控制羊肉产仔数有关。我们在受精卵中使用CRISPR-Cas9介导的基因编辑删除了Actl7b基因。初步结果支持ACTL7b是精子发生所必需的假设。缺乏Actl7b的雄性动物不育，在精子发生过程中表现出发育停滞。为了充分了解所观察到的表型，我们现在建议使用经典组织学，免疫组织化学，质量和质量对ACTL7b缺陷小鼠进行详细分析。规格和CoIP分析。有了这个，我们能够准确地描述ACTL7b在精子发生特别是男性因素不育的背景下的功能和作用。