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学科主题: 临床医学
题名:
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
作者: 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
发表日期: 2013-08-01
DOI: 10.1371/journal.pgen.1003645
卷: 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
所属项目编号: KSCX2-YW-R-081 ; 31071271 ; 31071018 ; CXB201005250017A ; CA34936 ; DK069599 ; CA09843 ; RP100329 ; RP110324 ; 2011CB944303 ; 2013CB945001
项目资助者: CAS Innovation Project ; National Natural Science Foundation of China ; Promotion Program for Shenzhen Key Laboratory ; NIH ; NIH (CPRIT grants)
WOS记录号: WOS:000323830300011
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/66717
Appears in Collections:北京大学深圳医院_期刊论文

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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

Recommended Citation:
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).
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