Loss of Axdnd1 causes sterility due to impaired spermatid differentiation in mice.
Loss of Axdnd1 causes sterility due to impaired spermatid differentiation in mice.
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DOI：
10.1002/rmb2.12452
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发表时间：
2022-01
影响因子：
3.4
通讯作者：
Tanemura K
中科院分区：
文献类型：
--
作者：
Hiradate Y;Harima R;Yanai R;Hara K;Nagasawa K;Osada M;Kobayashi T;Matsuyama M;Kanno SI;Yasui A;Tanemura K
精子发生是精子头部形态变形和鞭毛形成的过程，是精子所特有的现象。轴丝动力蛋白轻链蛋白定位于精子鞭毛，并且已知参与精子运动。在这里，我们专注于基因轴丝动力蛋白轻链结构域包含1（Axdnd 1），目的是确定其蛋白产物AXDND 1的功能。为了阐明AXDND 1在精子发生中的作用，我们使用CRISPR/Cas9系统产生了AxDND 1敲除（KO）小鼠。对生成的小鼠进行生育力测试并通过免疫组织化学进行分析。Axdnd 1 KO小鼠表现出由延伸步骤期间精子形成受损以及精子形成所必需的异常核成形和肩突引起的不育。此外，AXDND 1显示出丰富的睾丸表达，并定位于从粗线期中期精母细胞到早期精子细胞。 Axdnd 1是小鼠睾丸精子发生所必需的。这些发现提高了我们对精子发生和相关缺陷的了解。根据最近的一份报告，在非梗阻性无精子症（NOA）患者中发现了AXDND 1的有害杂合突变。因此，Axdnd 1基因敲除小鼠可以作为NOA的模型系统，为今后的NOA治疗研究提供了重要的实验依据。AXDND 1在精子发生早期的表达对生精小管不同阶段的观察表明，从精母细胞到细长精子细胞，该蛋白质都在细胞质中表达。
Spermiogenesis, the process of deformation of sperm head morphology and flagella formation, is a phenomenon unique to sperm. Axonemal dynein light chain proteins are localized to sperm flagella and are known to be involved in sperm motility. Here, we focused on the gene axonemal dynein light chain domain containing 1 (Axdnd1) with the aim to determine the function of its protein product AXDND1. To elucidate the role of AXDND1 in spermatogenesis, we generated Axdnd1 knockout (KO) mice using the CRISPR/Cas9 system. The generated mice were subjected to fertility tests and analyzed by immunohistochemistry. The Axdnd1 KO mouse exhibited sterility caused by impaired spermiogenesis during the elongation step as well as abnormal nuclear shaping and manchette, which are essential for spermiogenesis. Moreover, AXDND1 showed enriched testicular expression and was localized from the mid‐pachytene spermatocytes to the early spermatids. Axdnd1 is essential for spermatogenesis in the mouse testes. These findings improve our understanding of spermiogenesis and related defects. According to a recent report, deleterious heterozygous mutations in AXDND1 were found in non‐obstructive azoospermia (NOA) patients. Therefore, Axdnd1 KO mice could be used as a model system for NOA, which will greatly contribute to future NOA treatment studies. AXDND1 expression in early spermiogenesis. Observations of different stages of seminiferous tubules demonstrated cytoplasmic expression of the protein from spermatocytes to elongated spermatids.
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影响因子：
2.7
作者：
Nozawa, Yoko Ines;Yao, Erica;Gacayan, Rhodora;Xu, Shan-Mei;Chuang, Pao-Tien
通讯作者：
Chuang, Pao-Tien
影响因子：
3.3
作者：
San Agustin JT;Pazour GJ;Witman GB
通讯作者：
Witman GB
影响因子：
3.6
作者：
Shima, JE;McLean, DJ;Griswold, MD
通讯作者：
Griswold, MD
影响因子：
7
作者：
Indu, Sivankutty;Sekhar, Sreeja C.;Kumar, Pradeep G.
通讯作者：
Kumar, Pradeep G.
影响因子：
4.1
作者：
Lehti, Mari S.;Kotaja, Noora;Sironen, Anu
通讯作者：
Sironen, Anu