Restoration of spermatogenesis and male fertility using an androgen receptor transgene.
Restoration of spermatogenesis and male fertility using an androgen receptor transgene.
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DOI：
10.1371/journal.pone.0120783
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Jeyasuria P
中科院分区：
文献类型：
--
作者：
Walker WH;Easton E;Moreci RS;Toocheck C;Anamthathmakula P;Jeyasuria P
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Androgens signal through the androgen receptor (AR) to regulate male secondary sexual characteristics, reproductive tract development, prostate function, sperm production, bone and muscle mass as well as body hair growth among other functions. We developed a transgenic mouse model in which endogenous AR expression was replaced by a functionally modified AR transgene. A bacterial artificial chromosome (BAC) was constructed containing all AR exons and introns plus 40 kb each of 5' and 3' regulatory sequence. Insertion of an internal ribosome entry site and the EGFP gene 3’ to AR allowed co-expression of AR and EGFP. Pronuclear injection of the BAC resulted in six founder mice that displayed EGFP production in appropriate AR expressing tissues. The six founder mice were mated into a Sertoli cell specific AR knockout (SCARKO) background in which spermatogenesis is blocked at the meiosis stage of germ cell development. The AR-EGFP transgene was expressed in a cyclical manner similar to that of endogenous AR in Sertoli cells and fertility was restored as offspring were produced in the absence of Sertoli cell AR. Thus, the AR-EGFP transgene under the control of AR regulatory elements is capable of rescuing AR function in a cell selective, AR-null background. These initial studies provide proof of principle that a strategy employing the AR-EGFP transgene can be used to understand AR functions. Transgenic mice expressing selective modifications of the AR-EGFP transgene may provide crucial information needed to elicit the molecular mechanisms by which AR acts in the testis and other androgen responsive tissues.
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影响因子：
4.8
作者：
BREMNER, WJ;MILLAR, MR;SAUNDERS, PTK
通讯作者：
SAUNDERS, PTK
影响因子：
2.5
作者：
Chandler, Kelly J.;Chandler, Ronald L.;Mortlock, Douglas P.
通讯作者：
Mortlock, Douglas P.
影响因子：
4.6
作者：
Holdcraft, RW;Braun, RE
通讯作者：
Braun, RE
DOI：
10.1073/pnas.0506084102
发表时间：
2005-11-15
影响因子：
11.1
作者：
Meng, J;Holdcraft, RW;Braun, RE
通讯作者：
Braun, RE
影响因子：
16.2
作者：
Sopher, BL;Thomas, PS;La Spada, AR
通讯作者：
La Spada, AR