CDX-1 and CDX-2 are expressed in human colonic mucosa and are down-regulated in patients with Hirschsprung's disease associated enterocolitis

Caudal type homeobox gene-1 and -2 (CDX-1 and CDX-2), homologues of the Dro sophila homeobox gene caudal, encode transcription factors in endoderm. der ived tissues of the intestine. CDX genes control proliferation and differen tiation of intestinal mucosal cells and colon cancer cells. Hirschsprung's Disease (HD) or congenital intestinal aganglionosis, a major developmental anomaly of intestine, which causes functional intestinal obstruction, is fr equently associated with enterocolitis. Aetiology of HD-associated enteroco litis (HDEC) remains obscure. Reduction of gut mucosal enteroendocrine cell s, and inefficient transfer of the secretory immunoglobulin A across the gu t mucosal cell were shown to be associated with enterocolitis in HD patient s suggesting that mucosa may directly involve in the pathophysiology of HDE C. This study aims to ascertain whether the CDX-1 and CDX-2 genes, that con trol the proliferation and differentiation of mucosal cells, play a role in HDEC. Using semi-quantitative reverse transcription-polymerase chain react ion (RT-PCR) and in situ hybridisation, we analysed the expression of CDX-1 and CDX-2 genes in colon specimens of normal controls, necrotising enteroc olitis (NEC) infants, and HD patients with and without enterocolitis. We sh owed for the first time that CDX-1 and CDX-2 genes were expressed in the co lonic mucosal epithelium in normal, NEC and in HD infants. However, the exp ressions of both genes were reduced in patients with HDEC. Our findings sug gest that reduced expression of CDX-1 and CDX-2 genes in mucosa may be asso ciated with the development of HDEC. (C) 2001 Elsevier Science BY. All righ ts reserved.