A NOVEL PATHOGENESIS OF MEGACOLON IN NCX HOX11L.1 DEFICIENT MICE/

The Ncx/Hox11L.1 gene, a member of the Hox11 homeobox gene family, is mainly expressed in neural crest-derived tissues. To elucidate the rol e of Ncx/Hox11L.1, the gene has been inactivated in embryonic stem cel ls by homologous recombination. The homozygous mutant mice were viable . These mice developed megacolon with enteric ganglia by age 3-5 wk. H istochemical analysis of the ganglia revealed that the enteric neurons hyperinnervated in the narrow segment of megacolon. Some of these neu ronal cells degenerated and neuronal cell death occurred in later stag es. We propose that Ncx/Hox11L.1 is required for maintenance of proper functions of the enteric nervous system. These mutant mice can be use d to elucidate a novel pathogenesis for human neuronal intestinal dysp lasia.