Altered testicular gene expression patterns in mice lacking the polyubiquitin gene Ubb.
Altered testicular gene expression patterns in mice lacking the polyubiquitin gene Ubb.
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DOI：
10.1002/mrd.21318
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发表时间：
2011-06
影响因子：
2.5
通讯作者：
Ryu, Kwon-Yul
中科院分区：
文献类型：
--
作者：
Sinnar, Shamim A.;Small, Christopher L.;Evanoff, Ryan M.;Reinholdt, Laura G.;Griswold, Michael D.;Kopito, Ron R.;Ryu, Kwon-Yul
泛素（Ubiquitin, Ub）是存在于所有真核细胞中的一种必需蛋白，在包括生殖细胞发育在内的多种细胞功能中起着重要作用。我们之前曾报道过，多泛素基因Ubb的靶向破坏导致Ubb - / -小鼠的雄性和雌性不育，生殖细胞在减数分裂前期被抑制。尽管生殖细胞中Ub水平的降低被认为是导致Ubb - / -小鼠生育缺陷的原因，但Ub水平的降低如何导致不育仍不清楚。在这里，我们描述了小鼠睾丸转录组的微阵列分析结果，该结果表明Ubb - / -小鼠的基因表达模式发生了显著改变，可能与组蛋白2A （H2A）泛素化水平降低有关。我们发现大量与生育、代谢、转录和泛素-蛋白酶体系统（UPS）相关的基因在Ubb - / -小鼠中被错误调控。基因表达的如此广泛的改变表明，Ubb基因的缺失并不模仿单基因缺陷表型，而是可能影响更广泛的基因表达。这些基因表达的巨大变化，至少在一定程度上，促成了这些小鼠复杂的生育能力和代谢表型。
Ubiquitin (Ub) is an essential protein found in all eukaryotic cells and plays important roles in a variety of cellular functions including germ cell development. We have previously reported that targeted disruption of the polyubiquitin gene Ubb results in male and female infertility in Ubb−/− mice, with germ cells arrested at meiotic prophase I. Although reduced Ub levels in germ cells are believed to be responsible for the fertility defect in Ubb−/− mice, it is still unclear how reduced Ub levels result in sterility. Here we describe the results of a microarray analysis of the murine testicular transcriptome, which demonstrates dramatically altered gene expression patterns in Ubb−/− mice, possibly related to reduced levels of histone 2A (H2A) ubiquitylation. We find that large numbers of genes related to fertility, metabolism, transcription, and the ubiquitin–proteasome system (UPS) are misregulated in Ubb−/− mice. Such wide-ranging alterations in gene expression suggest that loss of the Ubb gene does not mimic a single-gene defect phenotype, but instead may affect gene expression more globally. These dramatic changes in gene expression could, at least in part, contribute to the complex fertility and metabolic phenotypes seen in these mice.
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影响因子：
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