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.

配子形成期间的缺陷可能阻碍成功的受精，从而导致不育。不孕症在临床上被定义为“生殖系统的疾病，该疾病是由于未能在12个月或更长时间以上定期不受保护的性交中未能实现临床怀孕的定义。已经描述了多个因素。曾描述多个因素会导致男性的不孕症，包括遗传畸变，包括环境影响，以及在男性的37-58％中，无论是在37-58％的疾病中，无论是在不知情的情况下还是不知情。技术（ART）有必要对男配子的形成涉及的基因和途径进行详细的理解，据描述肌动蛋白样蛋白7b（ACTL7B）在圆形测试中特异性表达，并且仅在促成的精子中，仅在4个Polymerphism中表现出来。此外，在沼泽水牛中对精子发生重要的基因中检测到了ACTL7B，并且似乎参与了羊肉中的垃圾大小。我们使用Zygotes中的CRISPR-CAS9介导的基因编辑删除了ACTL7B基因。初步结果支持精子发生所需的ACTL7B的假设。缺乏ACTL7B的雄性动物是不育的，在精子发生过程中显示出发育停滞。为了充分理解观察到的表型，我们现在提出了使用经典组织学，免疫组织化学，Mass。SPEC和COIP分析对ACTL7B缺陷小鼠进行详细分析。因此，我们能够精确地描述Actl7b在精子发生的背景下，尤其是男性因素不育症的背景下的功能和作用。