Smith C A, Clifford V, Western P S, Wilcox S A, Bell K S, Sinclair A H
Department of Paediatrics and Centre for Hormone Research, The University of Melbourne, Royal Children's Hospital, Melbourne, Victoria 3052, Australia.
J Mol Endocrinol. 2000 Feb;24(1):23-32. doi: 10.1677/jme.0.0240023.
DAX1 is an unusual member of the orphan nuclear receptor family of transcription factors. Mutations in human DAX1 cause X-linked adrenal hypoplasia congenita, while abnormal duplication of the gene is responsible for male-to-female dosage-sensitive sex reversal. Based on these and other observations, DAX1 is thought to play a role in adrenal and gonadal development in mammals. As DAX1 has not previously been described in any other vertebrate, a putative avian DAX1 clone was isolated from an embryonic chicken (Gallus domesticus) urogenital ridge cDNA library. The expression profile of this cDNA was then examined during gonadogenesis. The clone included the conserved 3' ligand-binding motif identified in humans and mice but the 5' region lacked the repeat motif thought to specify a DNA-binding domain in mammals. Southern blot analysis and fluorescence in situ hybridisation mapping showed that the gene is autosomal, located on chromosome 1q. Sequence comparisons showed that the putative chicken DAX1 protein has 63 and 60% identity with the human and mouse proteins respectively over the region of the conserved ligand-binding domain. However, stronger identity (74%) exists with a putative alligator DAX1 sequence over the same region. Northern blotting detected a single 1.4 kb transcript in late embryonic chicken gonads, while RNase protection assays revealed expression in the embryonic gonads of both sexes during the period of sexual differentiation. Expression increased in both sexes during gonadogenesis, but was higher in females than in males. This is the first description of a DAX1 homologue in a non-mammalian vertebrate.
DAX1是转录因子孤儿核受体家族中的一个特殊成员。人类DAX1基因的突变会导致X连锁先天性肾上腺发育不全，而该基因的异常复制则会导致男性向女性的剂量敏感性性反转。基于这些及其他观察结果，人们认为DAX1在哺乳动物的肾上腺和性腺发育中发挥作用。由于此前在任何其他脊椎动物中均未描述过DAX1，因此从胚胎期鸡（家鸡）的泌尿生殖嵴cDNA文库中分离出了一个假定的禽类DAX1克隆。随后在性腺发生过程中检测了该cDNA的表达谱。该克隆包含在人类和小鼠中鉴定出的保守的3'配体结合基序，但5'区域缺乏被认为在哺乳动物中指定DNA结合域的重复基序。Southern印迹分析和荧光原位杂交图谱显示该基因是常染色体基因，位于1号染色体的q臂上。序列比较表明，假定的鸡DAX1蛋白在保守配体结合域区域与人类和小鼠蛋白的同一性分别为63%和60%。然而，在同一区域与假定的短吻鳄DAX1序列存在更强的同一性（74%）。Northern印迹在胚胎后期鸡性腺中检测到单一的1.4 kb转录本，而核糖核酸酶保护分析揭示在性别分化期间两性胚胎性腺中均有表达。在性腺发生过程中两性的表达均增加，但雌性高于雄性。这是首次在非哺乳动物脊椎动物中描述DAX1同源物。
