IR@PKUHSC  > 北京大学深圳医院
学科主题临床医学
The Wilms Tumor Gene, Wt1, Is Critical for Mouse Spermatogenesis via Regulation of Sertoli Cell Polarity and Is Associated with Non-Obstructive Azoospermia in Humans
Wang, Xiao Na1,2; Li, Ze Song3,4; Ren, Yu1,2; Jiang, Tao5; Wang, Ya Qing6; Chen, Min1; Zhang, Jun1,2; Hao, Jian Xiu1,2; Wang, Yan Bo1,2; Sha, Ri Na1,2; Huang, Yi3,7; Liu, Xiao5; Hu, Jing Chu5; Sun, Guang Qing5; Li, Hong Gang8; Xiong, Cheng Liang8; Xie, Jun3; Jiang, Zhi Mao3; Cai, Zhi Ming3,7; Wang, Jun5; Wang, Jian5; Huff, Vicki9,10,11; Gui, Yao Ting3; Gao, Fei1
刊名PLOS GENETICS
2013-08-01
DOI10.1371/journal.pgen.1003645
9期:8
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Genetics & Heredity
研究领域[WOS]Genetics & Heredity
关键词[WOS]BLOOD-TESTIS BARRIER ; MALE-INFERTILITY ; EPITHELIAL TRANSFORMATION ; METANEPHRIC MESENCHYME ; HOMOZYGOUS MUTATION ; DEVELOPING KIDNEY ; MICE ; EXPRESSION ; POLYPEPTIDE ; JUNCTIONS
英文摘要

Azoospermia is one of the major reproductive disorders which cause male infertility in humans; however, the etiology of this disease is largely unknown. In the present study, six missense mutations of WT1 gene were detected in 529 human patients with non-obstructive azoospermia (NOA), indicating a strong association between WT1 mutation and NOA. The Wilms tumor gene, Wt1, is specifically expressed in Sertoli cells (SCs) which support spermatogenesis. To examine the functions of this gene in spermatogenesis, Wt1 was deleted in adult testis using Wt1(flox) and Cre-ER (TM) mice strains. We found that inactivation of Wt1 resulted in massive germ cell death and only SCs were present in most of the seminiferous tubules which was very similar to NOA in humans. In investigating the potential mechanism for this, histological studies revealed that the blood-testis barrier (BTB) was disrupted in Wt1 deficient testes. In vitro studies demonstrated that Wt1 was essential for cell polarity maintenance in SCs. Further studies found that the expression of cell polarity associated genes (Par6b and E-cadherin) and Wnt signaling genes (Wnt4, Wnt11) were downregulated in Wt1 deficient SCs, and that the expression of Par6b and E-cadherin was regulated by Wnt4. Our findings suggest that Wt1 is important in spermatogenesis by regulating the polarity of SCs via Wnt signaling pathway and that WT1 mutation is one of the genetic causes of NOA in humans.

语种英语
WOS记录号WOS:000323830300011
项目编号KSCX2-YW-R-081 ; 31071271 ; 31071018 ; CXB201005250017A ; CA34936 ; DK069599 ; CA09843 ; RP100329 ; RP110324 ; 2011CB944303 ; 2013CB945001
资助机构CAS Innovation Project ; National Natural Science Foundation of China ; Promotion Program for Shenzhen Key Laboratory ; NIH ; NIH (CPRIT grants)
引用统计
被引频次:33[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/66717
专题北京大学深圳医院
作者单位1.Chinese Acad Sci, Inst Zool, State Key Lab Reprod Biol, Beijing, Peoples R China
2.Univ Chinese Acad Sci, Beijing, Peoples R China
3.Peking Univ, Guangdong & Shenzhen Key Lab Male Reprod Med & Ge, Shenzhen PKU HKUST Med Ctr, Inst Urol,Shenzhen Hosp, Shenzhen, Peoples R China
4.Shenzhen Univ, Shenzhen Key Lab Genitourinary Tumor, Shenzhen Peoples Hosp 2, Affiliated Hosp 1, Shenzhen, Peoples R China
5.Beijing Genom Inst Shenzhen, Shenzhen, Peoples R China
6.Chinese Acad Sci, Key Lab Mol & Dev Biol, Inst Genet & Dev Biol, Beijing, Peoples R China
7.Shenzhen Univ, Shenzhen Peoples Hosp 2, Affiliated Hosp 1, Shenzhen, Peoples R China
8.Huazhong Univ Sci & Technol, Ctr Reprod Med, Tongji Med Coll, Wuhan 430074, Peoples R China
9.Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA
10.Univ Texas Houston, Grad Program Human Mol Genet, Houston, TX USA
11.Univ Texas Houston, Grad Program Genes & Dev, Houston, TX USA
推荐引用方式
GB/T 7714
Wang, Xiao Na,Li, Ze Song,Ren, Yu,et al. The Wilms Tumor Gene, Wt1, Is Critical for Mouse Spermatogenesis via Regulation of Sertoli Cell Polarity and Is Associated with Non-Obstructive Azoospermia in Humans[J]. PLOS GENETICS,2013,9(8).
APA Wang, Xiao Na.,Li, Ze Song.,Ren, Yu.,Jiang, Tao.,Wang, Ya Qing.,...&Gao, Fei.(2013).The Wilms Tumor Gene, Wt1, Is Critical for Mouse Spermatogenesis via Regulation of Sertoli Cell Polarity and Is Associated with Non-Obstructive Azoospermia in Humans.PLOS GENETICS,9(8).
MLA Wang, Xiao Na,et al."The Wilms Tumor Gene, Wt1, Is Critical for Mouse Spermatogenesis via Regulation of Sertoli Cell Polarity and Is Associated with Non-Obstructive Azoospermia in Humans".PLOS GENETICS 9.8(2013).
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