Kobayashi Akio, Chang Hao, Chaboissier Marie-Christine, Schedl Andreas, Behringer Richard R
Department of Molecular Genetics, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
Ann N Y Acad Sci. 2005 Dec;1061:9-17. doi: 10.1196/annals.1336.003.
Sox9 is an Sry-box-containing gene that encodes a transcriptional activator. During mouse gonadogenesis, Sox9 is detected in the male gonad at 11.5 days postcoitus (dpc). At 12.5 dpc, testicular cords form, morphologically distinguishing the male gonad from the ovary. From this stage onwards, Sox9 expression is restricted to the Sertoli cell lineage and persists in the adult. Humans with heterozygous mutations in SOX9 develop a skeletal syndrome known as campomelic dysplasia. Furthermore, most XY SOX9 heterozygotes show variable male-to-female sex reversal, implicating SOX9 in testis development. Sox9 heterozygous knockout mice die at birth with a syndrome similar to that of human campomelic dysplasia. In contrast to humans, XY Sox9+/- mice form normal appearing testes. Germ-line knockout of Sox9 using a conditional null allele provides a tool for generating Sox9-/- mice by simple genetic crosses. However, Sox9-/- mice die soon after 11.5 dpc because of cardiovascular defects. In vitro culture of the urogenital ridges of XY Sox9-/- results in gonads lacking testicular cords and Sertoli cell marker expression, but with the expression of ovarian-specific markers. Therefore, Sox9 is essential for diverting an intrinsically ovarian program of organogenesis toward testis formation.
Sox9是一个含有Sry盒的基因，编码一种转录激活因子。在小鼠性腺发育过程中，交配后11.5天（dpc）在雄性性腺中可检测到Sox9。在12.5 dpc时，睾丸索形成，在形态上使雄性性腺与卵巢区分开来。从这个阶段开始，Sox9的表达局限于支持细胞谱系，并在成年期持续存在。SOX9发生杂合突变的人类会患一种称为弯肢侏儒症的骨骼综合征。此外，大多数XY型SOX9杂合子表现出不同程度的男性向女性性反转，这表明SOX9参与睾丸发育。Sox9杂合敲除小鼠出生时死亡，患有与人类弯肢侏儒症相似的综合征。与人类不同，XY型Sox9+/-小鼠形成外观正常的睾丸。使用条件性无效等位基因对Sox9进行生殖系敲除，为通过简单的遗传杂交产生Sox9-/-小鼠提供了一种工具。然而，Sox9-/-小鼠在11.5 dpc后不久因心血管缺陷而死亡。对XY型Sox9-/-小鼠的泌尿生殖嵴进行体外培养，结果显示性腺缺乏睾丸索和支持细胞标志物表达，但表达卵巢特异性标志物。因此，Sox9对于将内在的卵巢器官发生程序转向睾丸形成至关重要。
