Herbarth B, Pingault V, Bondurand N, Kuhlbrodt K, Hermans-Borgmeyer I, Puliti A, Lemort N, Goossens M, Wegner M
Zentrum für Molekulare Neurobiologie, Universität Hamburg, 20246 Hamburg, Germany.
Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):5161-5. doi: 10.1073/pnas.95.9.5161.
The spontaneous mouse mutant Dominant megacolon (Dom) is a valuable model for the study of human congenital megacolon (Hirschsprung disease). Here we report that the defect in the Dom mouse is caused by mutation of the gene encoding the Sry-related transcription factor Sox10. This assignment is based on (i) colocalization of the Sox10 gene with the Dom mutation on chromosome 15; (ii) altered Sox10 expression in the gut and in neural-crest derived structures of cranial ganglia of Dom mice; (iii) presence of a frameshift in the Sox10 coding region, and (iv) functional inactivation of the resulting truncated protein. These results identify the transcriptional regulator Sox10 as an essential factor in mouse neural crest development and as a further candidate gene for human Hirschsprung disease, especially in cases where it is associated with features of Waardenburg syndrome.
自发性小鼠突变体显性巨结肠（Dom）是研究人类先天性巨结肠（ Hirschsprung病）的宝贵模型。在此我们报告，Dom小鼠的缺陷是由编码Sry相关转录因子Sox10的基因突变引起的。这一结论基于以下几点：（i）Sox10基因与15号染色体上的Dom突变共定位；（ii）Dom小鼠肠道及颅神经节神经嵴衍生结构中Sox10表达改变；（iii）Sox10编码区存在移码突变；（iv）所产生的截短蛋白功能失活。这些结果表明转录调节因子Sox10是小鼠神经嵴发育的必需因子，也是人类Hirschsprung病的另一个候选基因，特别是在与Waardenburg综合征特征相关的病例中。
