The role of Sox8 in sex determination and human disease

Sox8 在性别决定和人类疾病中的作用

• 批准号: nhmrc : 143101
• 负责人: Prof Peter Koopman
• 金额: $ 14.1万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2001
• 资助国家: 澳大利亚
• 起止时间: 2001-01-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/role-sox8-sex-human-disease/99640
• 关键词: role; Sox8; sex; determination; human

We have discovered a new gene called Sox8. This gene is very closely related to another gene, Sox9, that is known to be a critical factor in determining whether an embryo develops as a male or female by specifying whether the embryo makes testes or ovaries. We have found that Sox8, like Sox9, is active in the cell type in fetal testes known to be important for the development of maleness, at around the time when the male-female decision is being made. We therefore believe that Sox8 is an important part of the genetic chain of events leading to normal male development. We aim to study how Sox8 exerts its effects on male development. We have also found that in humans, Sox8 is located in a chromosomal region associated with a developmental disease syndrome characterized by mental retardation, facial defects and anomalies of male sexual development. Sox8 is active in mouse embryos in all the tissues affected by the human disease. We believe defects in SOX8 in humans are largely responsible for this disease, called ATR-16 syndrome. We will test whether patients with ATR-16 have defects involving SOX8 in their DNA in order to test this theory. In summary, we believe we have found a new human disease gene which will further our understanding of how developmental diseases arise in the embryo. In addition, this work will shed light on the process of sexual development, a significant healthcare problem in view of the fact that defects in sexual development are among the most common forms of birth defects.

我们发现了一种名为Sox8的新基因。这个基因与另一个基因Sox9有非常密切的关系，Sox9被认为是决定胚胎是作为男性还是女性发育的关键因素，因为它决定了胚胎是生成睾丸还是卵巢。我们发现，Sox8和Sox9一样，在胎儿睾丸中活跃的细胞类型中，已知对男性的发展很重要，大约在男性和女性做出决定的时候。因此，我们认为Sox8是导致正常男性发育的遗传链的重要组成部分。我们的目标是研究Sox8对男性发育的影响。我们还发现，在人类中，Sox8位于与一种以智力低下、面部缺陷和男性性发育异常为特征的发育疾病综合征相关的染色体区域。在受人类疾病影响的所有组织中，SOX8在小鼠胚胎中都是活跃的。我们认为，人类SOX8的缺陷是这种称为ATR-16综合征的疾病的主要原因。我们将测试ATR-16患者的DNA中是否存在涉及SOX8的缺陷，以测试这一理论。总而言之，我们相信我们已经发现了一种新的人类疾病基因，它将进一步加深我们对发育疾病如何在胚胎中产生的理解。此外，这项工作将揭示性发育的过程，鉴于性发育缺陷是最常见的出生缺陷形式之一，这是一个重大的医疗保健问题。