Cbx2, a Polycomb Group Gene, Is Required for Sry Gene Expression in Mice

Cbx2, a Polycomb Group Gene, Is Required for Sry Gene Expression in Mice
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DOI:
10.1210/en.2011-1055
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发表时间:
2012-02-01
期刊:
影响因子:
4.8
通讯作者:
Morohashi, Ken-ichirou
Morohashi, Ken-ichirou
中科院分区:
医学2区
文献类型:
--
作者:
Katoh-Fukui, Yuko;Miyabayashi, Kanako;Morohashi, Ken-ichirou

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缺乏多梳组蛋白CBX 2(染色体盒同源物2;也称为M33)功能的小鼠表现出性腺、肾上腺和脾脏发育的缺陷。特别是,XY敲除(KO)小鼠发育卵巢,但不睾丸,性腺发育不全的两种性别。然而,CBX 2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和免疫组化分析表明,Sry,Sox 9,Lhx 9,Ad 4 BP/SF-1,Dax-1,Gata 4,Arx和Dmrt 1,基因编码的转录因子性腺发育所必需的,在Cbx 2 KO性腺的表达受到影响。通过将Cbx 2 KO小鼠与显示Sry或Sox 9强制表达的转基因小鼠杂交,挽救了Cbx 2 KO小鼠中的雄性至雌性性逆转。然而,这些小鼠的睾丸仍然发育不全,这表明性腺的大小和性别是由不同的基因决定的。我们的研究暗示Cbx 2通过调节Sry基因表达参与睾丸分化。(内分泌学153:913-924,2012)
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. (Endocrinology 153: 913-924, 2012)