Journal article
Gene expression alterations by conditional knockout of androgen receptor in adult Sertoli cells of Utp14b jsd/jsd (jsd) mice
Biology of reproduction, Vol.84(2), pp.400-408
02/2011
Handle:
https://hdl.handle.net/2376/100690
PMID: 21312389
Abstract
Spermatogenesis is dependent primarily on testosterone action on the Sertoli cells, but the molecular mechanisms have not been identified. Attempts to identify testosterone-regulated target genes in Sertoli cells have used microarray analysis of gene expression in mice lacking the androgen receptor (AR) in Sertoli cells (SCARKO) and wild-type mice, but the analyses have been complicated both by alteration of germ cell composition of the testis when pubertal or adult mice were used and by differences in Sertoli-cell gene expression from the expression in adults when prepubertal mice were used. To overcome these limitations and identify AR-regulated genes in adult Sertoli cells, we compared gene expression in adult jsd (Utp14b jsd/jsd, juvenile spermatogonial depletion) mouse testes and with that in SCARKO-jsd mouse testes, since their cellular compositions are essentially identical, consisting of only type A spermatogonia and somatic cells. Microarray analysis identified 157 genes as downregulated and 197 genes as upregulated in the SCARKO-jsd mice compared to jsd mice. Some of the AR-regulated genes identified in the previous studies, including Rhox5, Drd4, and Fhod3, were also AR regulated in the jsd testes, but others, such as proteases and components of junctional complexes, were not AR regulated in our model. Surprisingly, a set of germ cell–specific genes preferentially expressed in differentiated spermatogonia and meiotic cells, including Meig1, Sycp3, and Ddx4, were all upregulated about 2-fold in SCARKO-jsd testes. AR-regulated genes in Sertoli cells must therefore be involved in the regulation of spermatogonial differentiation, although there was no significant differentiation to spermatocytes in SCARKO-jsd mice. Further gene ontogeny analysis revealed sets of genes whose changes in expression may be involved in the dislocation of Sertoli cell nuclei in SCARKO-jsd testes.
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Details
- Title
- Gene expression alterations by conditional knockout of androgen receptor in adult Sertoli cells of Utp14b jsd/jsd (jsd) mice
- Creators
- Wei Zhou - Department of Experimental Radiation Oncology, M.D. Anderson Cancer Center, Unit 066, 1515 Holcombe Blvd., Houston, TX 77030, USA. wzhou@mdanderson.orgGensheng WangChristopher L SmallZhilin LiuConnie C WengLizhong YangMichael D GriswoldMarvin L Meistrich
- Publication Details
- Biology of reproduction, Vol.84(2), pp.400-408
- Academic Unit
- Molecular Biosciences, School of
- Publisher
- United States
- Grant note
- R01 HD040397 / NICHD NIH HHS R37 HD010808 / NICHD NIH HHS P30 CA016672 / NCI NIH HHS R37 HD016229 / NICHD NIH HHS R01 HD016229 / NICHD NIH HHS HD-40397 / NICHD NIH HHS HD-16229 / NICHD NIH HHS CA 16672 / NCI NIH HHS R01 HD010808 / NICHD NIH HHS R56 HD016229 / NICHD NIH HHS HD-10808 / NICHD NIH HHS
- Identifiers
- 99900546536701842
- Language
- English
- Resource Type
- Journal article