Loss-of-function mutations in QRICH2 cause male infertility with multiple morphological abnormalities of the sperm flagella
| Autor: | Ke Wang, Xiaohui Jiang, Jianfeng Sun, Kai Sheng, Li Tang, Feng Zhang, Chuan Jiang, Xue Pei, Weiyu Li, Lanzhen Yan, Ying Shen, Mohan Liu, Juan Cheng, Wenling Tu, Xiang Wang, Haojuan Wu, Huanxun Yue, Shuying Li, Weiqi Kong, Fengyun Hu, Xueguang Zhang, Xiaoyu Yang, Xudong Zhao, J. Xu, Wenming Xu, Kailai Cai, Fuping Li, Guiping Yuan, Xiaoliang Li, Yihong Yang |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Infertility Sterility Science General Physics and Astronomy 02 engineering and technology Biology Flagellum Article General Biochemistry Genetics and Molecular Biology Male infertility 03 medical and health sciences medicine lcsh:Science Loss function Sperm motility Multidisciplinary General Chemistry 021001 nanoscience & nanotechnology medicine.disease Sperm Phenotype Cell biology 030104 developmental biology lcsh:Q 0210 nano-technology |
| Zdroj: | Nature Communications Nature Communications, Vol 10, Iss 1, Pp 1-15 (2019) |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-018-08182-x |
| Popis: | Aberrant sperm flagella impair sperm motility and cause male infertility, yet the genes which have been identified in multiple morphological abnormalities of the flagella (MMAF) can only explain the pathogenic mechanisms of MMAF in a small number of cases. Here, we identify and functionally characterize homozygous loss-of-function mutations of QRICH2 in two infertile males with MMAF from two consanguineous families. Remarkably, Qrich2 knock-out (KO) male mice constructed by CRISPR-Cas9 technology present MMAF phenotypes and sterility. To elucidate the mechanisms of Qrich2 functioning in sperm flagellar formation, we perform proteomic analysis on the testes of KO and wild-type mice. Furthermore, in vitro experiments indicate that QRICH2 is involved in sperm flagellar development through stabilizing and enhancing the expression of proteins related to flagellar development. Our findings strongly suggest that the genetic mutations of human QRICH2 can lead to male infertility with MMAF and that QRICH2 is essential for sperm flagellar formation. Multiple morphological abnormalities of the sperm flagella (MMAF) is a cause of male infertility. Here the authors identify homozygous nonsense mutations of the glutamine rich 2 (QRICH2) gene in two MMAF patients from 2 consanguineous families and show using QRICH2 knockout mice that the protein is required for sperm flagellar formation and motility. |
| Databáze: | OpenAIRE |
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