The role of Sox8 in sex determination and human disease

我们发现了一个新的基因，叫做Sox 8。该基因与另一个基因Sox 9非常密切相关，Sox 9已知是通过指定胚胎是否产生睾丸或卵巢来确定胚胎是否发育为男性或女性的关键因素。我们发现，Sox 8和Sox 9一样，在胎儿睾丸中的细胞类型中是活跃的，这种细胞类型对男性的发育很重要，大约在做出男女决定的时候。因此，我们认为Sox 8是导致正常男性发育的遗传事件链的重要组成部分。我们的目标是研究Sox 8如何发挥其对男性发育的影响。我们还发现，在人类中，Sox 8位于与发育疾病综合征相关的染色体区域，该发育疾病综合征的特征是智力迟钝、面部缺陷和男性性发育异常。Sox 8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SOX 8的缺陷在很大程度上导致了这种称为ATR-16综合征的疾病。我们将测试ATR-16患者的DNA中是否存在涉及SOX 8的缺陷，以验证这一理论。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胚胎中发育性疾病如何发生的理解。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形式之一。

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.