Abnormal expression and distribution of nidogen in Hirschsprung's disease

Hirschsprung's disease (congenital colonic aganglionosis) is associated with abnormalities in the distributions and amounts of basement membrane and other extracellular matrix components in the human gut. The authors have investigated the possible significance of nidogen in Hirschsprung's disease, because this glycoprotein is necessary for the formation of ternary complexes with the other basement membrane components, laminin and collagen type IV, and thus may contribute the pathology of the disease. Increased nidogen immunoreactivity in the smooth muscle basement membranes and muscularis mucosae of the distal aganglionic zone in Hirschsprung's bowel was observed, the nidogen immunoreactivity demonstrating that the thickness of the muscularis mucosae was increased in this region. However, steady-state nidogen mRNA levels were found to be significantly lower in both proximal and distal Hirschsprung's bowel (relative to controls). In contrast, no significant differences were observed in the steady-state levels of the mRNAs coding for laminin subunits. These results indicate that although abnormalities in the amount or distribution of nidogen may contribute to the abnormalities seen in the extracellular matrix in Hirschsprung's disease, the levels of expression of the genes coding for either nidogen or laminin are unlikely to be primarily responsible for the lesions.