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Testis determination requires insulin receptor family function in mice

机译:睾丸测定需要小鼠中的胰岛素受体家族功能

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In mice, gonads are formed shortly before embryonic day 10.5 by the thickening of the mesonephros and consist of somatic cells and migratory primordial germ cells. The male sex-determining process is set in motion by the sex-determining region of the Y chromosome (Sry), which triggers differentiation of the Sertoli cell lineage. In turn, Sertoli cells function as organizing centres and direct differentiation of the testis. In the absence of Sry expression, neither XX nor XY gonads develop testes, and alterations in Sry expression are often associated with abnormal sexual differentiation. The molecular signalling mechanisms by which Sry specifies the male pathway and models the undif-ferentiated gonad are unknown. Here we show that the insulin receptor tyrosine kinase family, comprising Ir, Igf1r and Irr, is required for the appearance of male gonads and thus for male sexual differentiation. XY mice that are mutant for all three receptors develop ovaries and show a completely female pheno-type. Reduced expression of both Sry and the early testis-specific marker Sox9 indicates that the insulin signalling pathway is required for male sex determination.
机译:在小鼠中,性腺是在胚胎第10.5天前不久由中肾变厚而形成的,由体细胞和迁徙的原始生殖细胞组成。男性性别决定过程由Y染色体的性别决定区域(Sry)启动,这触发了Sertoli细胞谱系的分化。反过来,支持细胞作为睾丸的组织中心和直接分化。在没有Sry表达的情况下,XX和XY性腺均不发育睾丸,并且Sry表达的改变通常与异常的性别分化有关。 Sry通过其指定男性途径并模拟未分化的性腺的分子信号传导机制尚不清楚。在这里,我们显示,包括Ir,Igf1r和Irr在内的胰岛素受体酪氨酸激酶家族对于男性性腺的出现并因此对于男性的性别分化是必需的。对所有三个受体都突变的XY小鼠会发育卵巢,并表现出完全雌性的表型。 Sry和早期睾丸特异性标志物Sox9的表达降低表明,确定男性性别需要胰岛素信号通路。

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