The role of Sox8 in sex determination and human disease

我们发现了一种叫做Sox8的新基因。这个基因与另一个基因Sox9密切相关，众所周知，Sox9是决定胚胎发育为男性还是女性的关键因素，它决定了胚胎是发育成睾丸还是卵巢。我们发现，Sox8和Sox9一样，在胎儿睾丸的一种细胞类型中很活跃，这种细胞类型对男性的发育很重要，大约在做出雄性和雌性决定的时候。因此，我们认为Sox8是导致男性正常发育的遗传链的重要组成部分。我们的目的是研究Sox8对男性发育的影响。我们还发现，在人类中，Sox8位于一个与发育性疾病综合征相关的染色体区域，该综合征以智力迟钝、面部缺陷和男性性发育异常为特征。Sox8在小鼠胚胎中受人类疾病影响的所有组织中都是活跃的。我们认为，人类SOX8的缺陷在很大程度上导致了这种被称为ATR-16综合征的疾病。为了验证这一理论，我们将测试ATR-16患者的DNA中是否存在涉及SOX8的缺陷。总之，我们相信我们已经发现了一个新的人类疾病基因，这将进一步加深我们对发育性疾病如何在胚胎中产生的理解。此外，这项工作将阐明性发育的过程，这是一个重要的保健问题，因为性发育缺陷是最常见的出生缺陷之一。

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.