Microvillus inclusion disease: A genetic defect affecting apical membrane protein traffic in intestinal epithelium

The striking similarities between microvillus inclusions (MIs) in enterocyt es in microvillus inclusion disease (MID) and vacuolar apical compartment i n tissue culture epithelial cells, led us to analyze endoscopic biopsies of duodenal mucosa of a patient after the samples were used for diagnostic pr ocedures. Samples from another patient with an unrelated disease were used as controls. The MID enterocytes showed a decrease in the thickness of the apical F-actin layer, and normal microtubules. The immunofluorescence analy sis of the distribution of five epical membrane markers (sucrase isomaltase , alkaline phosphatase, NHE-3 Na+/H+ exchanger, cGMP-dependent protein kina se, and cystic fibrosis trans-membrane conductance regulator), showed low l evels of these proteins in their standard localization at the apical membra ne as compared with normal duodenal epithelium processed in parallel. Inste ad, four of these markers were found in a diffuse distribution in the apica l cytoplasm, below the terminal web (as indicated by co-localization with F -actin and cytokeratin 19), and in Mis as well. The basolateral protein Na-K(-)ATPase, in contrast, was normally localized. These results support the hypothesis that MID may represent the first genetic defect affecting apica l membrane traffic, possibly in a late step of apical exocytosis.