Swain A, Narvaez V, Burgoyne P, Camerino G, Lovell-Badge R
Division of Developmental Genetics, MRC National Institute for Medical Research, London, UK.
Nature. 1998 Feb 19;391(6669):761-7. doi: 10.1038/35799.
DAX1, which encodes an unusual member of the nuclear hormone-receptor superfamily, is a gene that may be responsible for a sex-reversal syndrome in humans, referred to as dosage-sensitive sex reversal, in which XY individuals carrying duplications of Xp21, part of the small arm of the X chromosome, develop as females. XY mice carrying extra copies of mouse Dax1 as a transgene show delayed testis development when the gene is expressed at high levels, but do not normally show sex reversal. Complete sex reversal occurs, however, when the transgene is tested against weak alleles of the sex-determining Y-chromosome gene Sry. These results show that DAX1 is largely, if not solely, responsible for dosage-sensitive sex reversal and provide a model for early events in mammalian sex determination, when precise levels and timing of gene expression are critical.
DAX1编码核激素受体超家族中的一个特殊成员，该基因可能与人的性反转综合征有关，即剂量敏感性性反转，其中携带X染色体短臂Xp21重复片段的XY个体发育为女性。携带额外拷贝小鼠Dax1转基因的XY小鼠，当该基因高水平表达时，睾丸发育延迟，但通常不会出现性反转。然而，当转基因与性别决定Y染色体基因Sry的弱等位基因进行检测时，会发生完全性反转。这些结果表明，DAX1在很大程度上（如果不是唯一的话）导致了剂量敏感性性反转，并为哺乳动物性别决定的早期事件提供了一个模型，此时基因表达的精确水平和时间至关重要。
