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Rex1(Zfp42)基因敲除小鼠表现出睾丸功能受损、睾丸形态异常和基因表达异常。

Rex1 (Zfp42) null mice show impaired testicular function, abnormal testis morphology, and aberrant gene expression.

机构信息

Department of Pharmacology, Weill Cornell Medical College of Cornell University, 1300 York Avenue, New York, NY 10065, USA.

出版信息

Dev Biol. 2011 Aug 15;356(2):370-82. doi: 10.1016/j.ydbio.2011.05.664. Epub 2011 May 27.

Abstract

Rex1 (Zfp42), GeneID 132625, is a gene whose expression is closely associated with pluripotency/multipotency in both mouse and human embryonic stem cells. To study the function of the murine Rex1 gene in vivo, we have used cre/lox technology to create Rex1(floxed) mice and mice deficient in Rex1 gene function. Rex1(-/-)males are characterized by an age-associated decrease in sperm counts, abnormal sperm morphology, and mild testicular atrophy. We characterized global patterns of gene expression in primary germ cells by microarray and identified the growth hormone responsive gene, GRTP1, as a transcript present at a 4.5 fold higher level in wild type (WT) compared to Rex1(-/-) mice. We analyzed immature germ cell (Dazl), proliferating (PCNA), and Sertoli cell populations, and quantitated levels of apoptosis in Rex1(-/-) as compared to WT testes. We evaluated the expression of proteins previously reported to correlate with Rex1 expression, such as STAT3, phospho-STAT3, p38, and phospho-p38 in the testis. We report a distinct cellular localization of total STAT3 protein in Rex1(-/-) affected testes. Our data suggest that loss of Rex1 leads to impaired testicular function.

摘要

Rex1(Zfp42),基因 ID 132625,是一个在小鼠和人类胚胎干细胞中与多能性密切相关的基因。为了研究鼠 Rex1 基因在体内的功能,我们使用 cre/lox 技术构建了 Rex1(floxed)小鼠和 Rex1 基因功能缺失的小鼠。Rex1(-/-)雄性小鼠的特征是精子数量随年龄的增长而减少、精子形态异常和轻度睾丸萎缩。我们通过微阵列分析了初级生殖细胞的基因表达谱,发现生长激素反应基因 GRTP1 在野生型(WT)小鼠中的转录水平比 Rex1(-/-)小鼠高 4.5 倍。我们分析了不成熟的生殖细胞(Dazl)、增殖(PCNA)和支持细胞群体,并定量了 Rex1(-/-)与 WT 睾丸中的凋亡水平。我们评估了与 Rex1 表达相关的先前报道的蛋白质的表达,如 STAT3、磷酸化-STAT3、p38 和磷酸化-p38 在睾丸中的表达。我们报告了 Rex1(-/-)影响睾丸中总 STAT3 蛋白的独特细胞定位。我们的数据表明,Rex1 的缺失导致睾丸功能受损。

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