Mutation of the Sry-related
            <i>Sox10</i>
            gene in
            <i>Dominant megacolon</i>
            , 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

doi:10.1073/pnas.95.9.5161

<jats:p> The spontaneous mouse mutant <jats:italic>Dominant megacolon</jats:italic> ( <jats:italic>Dom</jats:italic> ) is a valuable model for the study of human congenital megacolon (Hirschsprung disease). Here we report that the defect in the <jats:italic>Dom</jats:italic> mouse is caused by mutation of the gene encoding the Sry-related transcription factor Sox10. This assignment is based on ( <jats:italic>i</jats:italic> ) colocalization of the <jats:italic>Sox10</jats:italic> gene with the <jats:italic>Dom</jats:italic> mutation on chromosome 15; ( <jats:italic>ii</jats:italic> ) altered <jats:italic>Sox10</jats:italic> expression in the gut and in neural-crest derived structures of cranial ganglia of <jats:italic>Dom</jats:italic> mice; ( <jats:italic>iii</jats:italic> ) presence of a frameshift in the Sox10 coding region, and ( <jats:italic>iv</jats:italic> ) 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. </jats:p>

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

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