Open AccessMutation of the Sry-related Sox10 gene in Dominant megacolon , a mouse model for human Hirschsprung disease
Author(s) -
Beate Herbarth,
Véronique Pingault,
Nadège Bondurand,
Kirsten Kuhlbrodt,
Irm HermansBorgmeyer,
Aldamaria Puliti,
N Lemort,
Michel Goossens,
Michael Wegner
Publication year - 1998
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.95.9.5161
Subject(s) - sox10 , megacolon , waardenburg syndrome , biology , testis determining factor , neural crest , frameshift mutation , genetics , mutant , gene , hirschsprung's disease , mutation , microbiology and biotechnology , pathology , medicine , phenotype , disease , y chromosome
The spontaneous mouse mutantDominant megacolon (Dom ) is a valuable model for the study of human congenital megacolon (Hirschsprung disease). Here we report that the defect in theDom mouse is caused by mutation of the gene encoding the Sry-related transcription factor Sox10. This assignment is based on (i ) colocalization of theSox10 gene with theDom mutation on chromosome 15; (ii ) alteredSox10 expression in the gut and in neural-crest derived structures of cranial ganglia ofDom 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.