Department of Aging Intervention, National Institute for Longevity Sciences, Obu 474-8511, Japan.
Endocrinology. 2012 Feb;153(2):913-24. doi: 10.1210/en.2011-1055. Epub 2011 Dec 20.
Mice lacking the function of the polycomb group protein CBX2 (chromobox homolog 2; also known as M33) show defects in gonadal, adrenal, and splenic development. In particular, XY knockout (KO) mice develop ovaries but not testes, and the gonads are hypoplastic in both sexes. However, how CBX2 regulates development of these tissues remains largely unknown. In the present study, we used microarray, RT-PCR, and immunohistochemical analyses to show that the expression of Sry, Sox9, Lhx9, Ad4BP/SF-1, Dax-1, Gata4, Arx, and Dmrt1, genes encoding transcription factors essential for gonadal development, is affected in Cbx2 KO gonads. Male-to-female sex reversal in Cbx2 KO mice was rescued by crossing them with transgenic mice displaying forced expression of Sry or Sox9. However, testes remained hypoplastic in these mice, indicating that the size and the sex of the gonad are determined by different sets of genes. Our study implicates Cbx2 in testis differentiation through regulating Sry gene expression.
缺乏多梳蛋白复合物 CBX2 功能的小鼠（chromobox homolog 2；也称为 M33）表现出性腺、肾上腺和脾脏发育缺陷。特别是 XY 敲除（KO）小鼠发育出卵巢而不是睾丸，并且两性的性腺均发育不良。然而，CBX2 如何调节这些组织的发育在很大程度上仍然未知。在本研究中，我们使用微阵列、RT-PCR 和免疫组织化学分析表明，Sry、Sox9、Lhx9、Ad4BP/SF-1、Dax-1、Gata4、Arx 和 Dmrt1 等基因的表达受到影响，这些基因编码的转录因子对于性腺发育至关重要。在 Cbx2 KO 小鼠中，通过与表达 Sry 或 Sox9 的转基因小鼠杂交，实现了雄性到雌性的性反转。然而，这些小鼠的睾丸仍然发育不良，这表明性腺的大小和性别由不同的基因决定。我们的研究表明，CBX2 通过调节 Sry 基因的表达参与睾丸分化。
