Functional analysis of Sox8 and Sox9 during sex determination in the mouse
Functional analysis of Sox8 and Sox9 during sex determination in the mouse
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DOI：
10.1242/dev.01087
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发表时间：
2004-05-01
期刊：
影响因子：
4.6
通讯作者：
Schedl, A
中科院分区：
文献类型：
--
作者：
Chaboissier, MC;Kobayashi, A;Schedl, A
哺乳动物的性别决定指导最初的双能性腺分化为睾丸或卵巢。这一决定是由性别决定基因Sry的表达触发的，这导致了男性特异性基因的激活，包括含有基因Sox9的HMG盒。从小鼠的转基因研究中可以清楚地看出，Sox 9足以诱导睾丸形成。然而，没有直接证实Sox 9在睾丸决定中的重要作用。这里提出的研究是Sox 9在介导从卵巢途径到睾丸途径的转换中发挥重要作用的第一个实验证据。使用条件性基因靶向，我们表明，纯合性缺失的XY性腺中的Sox 9干扰性索的发展和激活的男性特异性标记Mis和P450SCC，并导致女性特异性标记Bmp2和卵泡抑素的表达。此外，使用组织特异性敲除方法，我们表明，Sox 9参与支持细胞分化，激活Mis和Sox 8，和失活的Sry。最后，双敲除分析表明，Sox 8增强Sox 9在小鼠睾丸分化中的功能。
Sex determination in mammals directs an initially bipotential gonad to differentiate into either a testis or an ovary. This decision is triggered by the expression of the sex-determining gene Sry, which leads to the activation of male-specific genes including the HMG-box containing gene Sox9. From transgenic studies in mice it is clear that Sox9 is sufficient to induce testis formation. However, there is no direct confirmation for an essential role for Sox9 in testis determination. The studies presented here are the first experimental proof for an essential role for Sox9 in mediating a switch from the ovarian pathway to the testicular pathway. Using conditional gene targeting, we show that homozygous deletion of Sox9 in XY gonads interferes with sex cord development and the activation of the male-specific markers Mis and P450scc, and leads to the expression of the female-specific markers Bmp2 and follistatin. Moreover, using a tissue specific knock-out approach, we show that Sox9 is involved in Sertoli cell differentiation, the activation of Mis and Sox8, and the inactivation of Sry. Finally, double knock-out analyses suggest that Sox8 reinforces Sox9 function in testis differentiation of mice.