Mutation of the Sry-related Sox10 gene in Dominant megacolon, a mouse model for human Hirschsprung disease

Beate Herbarth, Veronique Pingault, Nadege Bondurand, Kirsten Kuhlbrodt, Irm Hermans-Borgmeyer, Aldamaria Puliti, Nicole Lemort, Michel Goossens, Michael Wegner

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)5161-5165
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number9
DOIs
Publication statusPublished - Apr 28 1998

Keywords

  • Glia
  • High-mobility-group domain
  • Neural crest
  • Transcription

ASJC Scopus subject areas

  • Genetics
  • General

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