Loss-of-function mutations in QRICH2 cause male infertility with multiple morphological abnormalities of the sperm flagella

doi:10.1038/ncomms14576

GSTDTAP > 资源环境科学

DOI	10.1038/ncomms14576
	Loss-of-function mutations in QRICH2 cause male infertility with multiple morphological abnormalities of the sperm flagella
	Shen, Ying 1; Zhang, Feng 2,3,4; Li, Fuping 5,6; Jiang, Xiaohui 5,6; Yang, Yihong 7; Li, Xiaoliang 1; Li, Weiyu 2; Wang, Xiang 1; Cheng, Juan 8; Liu, Mohan 9,10; Zhang, Xueguang 1; Yuan, Guiping 11; Pei, Xue 9,10; Cai, Kailai 12; Hu, Fengyun 13; Sun, Jianfeng 14; Yan, Lanzhen 15,16; Tang, Li 1; Jiang, Chuan 1; Tu, Wenling 9,10; Xu, Jinyan 5,6; Wu, Haojuan 8; Kong, Weiqi 1; Li, Shuying 1; Wang, Ke 1; Sheng, Kai 1; Zhao, Xudong 15,16,17; Yue, Huanxun 5,6; Yang, Xiaoyu 18; Xu, Wenming 1
	2019-01-25
发表期刊	NATURE COMMUNICATIONS
ISSN	2041-1723
出版年	2019
卷号	10
文章类型	Article
语种	英语
国家	Peoples R China; New Zealand
英文摘要	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.
领域	资源环境
收录类别	SCI-E
WOS记录号	WOS:000456696700009
WOS关键词	FIBROUS SHEATH ; PROTEIN ; MOTILITY ; DYNEIN ; GENES ; ASTHENOZOOSPERMIA ; LOCALIZATION ; POPULATION ; EXPRESSION ; ANOMALIES
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
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引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/203229
专题	资源环境科学
作者单位	1.Sichuan Univ, Key Lab Obstet Gynecol & Pediat Dis & Birth Defec, West China Univ Hosp 2,Dept Obstet Gynecol, Joint Lab Reprod Med SCU CUHK,Minist Educ, Chengdu 610041, Sichuan, Peoples R China; 2.Fudan Univ, Inst Metab & Integrat Biol, Sch Life Sci, Obstet & Gynecol Hosp, Shanghai 200011, Peoples R China; 3.Nanjing Med Univ, Sch Publ Hlth, Ctr Global Hlth, State Key Lab Reprod Med, Nanjing 211116, Jiangsu, Peoples R China; 4.Shanghai Key Lab Female Reprod Endocrine Related, Shanghai 200011, Peoples R China; 5.Sichuan Univ, West China Univ Hosp 2, Human Sperm Bank, Chengdu 610041, Sichuan, Peoples R China; 6.Sichuan Univ, Key Lab Birth Defects & Related Dis Women & Child, Minist Educ, Chengdu 610041, Sichuan, Peoples R China; 7.Sichuan Univ, Ctr Reprod Med, West China Univ Hosp 2, Chengdu 610041, Sichuan, Peoples R China; 8.Southwest Med Univ, Luzhou 646000, Peoples R China; 9.Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Dept Med Genet, Chengdu 610041, Sichuan, Peoples R China; 10.Collaborat Innovat Ctr, Chengdu 610041, Sichuan, Peoples R China; 11.Sichuan Univ, Analyt & Testing Ctr, Chengdu 610041, Sichuan, Peoples R China; 12.Chengdu Res Base Giant Panda Breeding, Chengdu 610041, Sichuan, Peoples R China; 13.Auckland Univ, Auckland 1142, New Zealand; 14.Chengdu Univ TCM, Teaching Hosp, Chengdu 610041, Sichuan, Peoples R China; 15.Chinese Acad Sci, Key Lab Anim Models & Human Dis Mech, Kunming 650000, Yunnan, Peoples R China; 16.Chinese Acad Sci, Kunming Inst Zool, Kunming 650000, Yunnan, Peoples R China; 17.Chinese Acad Sci, Ctr Excellence Anim Evolut & Genet, Kunming 650223, Yunnan, Peoples R China; 18.Nanjing Med Univ, Hosp 1, Clin Ctr Reprod Med, State Key Lab Reprod Med, Nanjing 210029, Jiangsu, Peoples R China
推荐引用方式 GB/T 7714	Shen, Ying,Zhang, Feng,Li, Fuping,et al. Loss-of-function mutations in QRICH2 cause male infertility with multiple morphological abnormalities of the sperm flagella[J]. NATURE COMMUNICATIONS,2019,10.
APA	Shen, Ying.,Zhang, Feng.,Li, Fuping.,Jiang, Xiaohui.,Yang, Yihong.,...&Xu, Wenming.(2019).Loss-of-function mutations in QRICH2 cause male infertility with multiple morphological abnormalities of the sperm flagella.NATURE COMMUNICATIONS,10.
MLA	Shen, Ying,et al."Loss-of-function mutations in QRICH2 cause male infertility with multiple morphological abnormalities of the sperm flagella".NATURE COMMUNICATIONS 10(2019).