1. Apical Membrane Alterations in Non-intestinal Organs in Microvillus Inclusion Disease
- Author
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Schlegel, Cameron, Weis, Victoria G, Knowles, Byron C, Lapierre, Lynne A, Martin, Martin G, Dickman, Paul, Goldenring, James R, and Shub, Mitchell D
- Subjects
Medical Physiology ,Biomedical and Clinical Sciences ,Digestive Diseases ,Genetics ,Clinical Research ,2.1 Biological and endogenous factors ,Aetiology ,Oral and gastrointestinal ,Cell Membrane ,Child ,Female ,Genetic Predisposition to Disease ,Humans ,Indians ,North American ,Infant ,Infant ,Newborn ,Kidney ,Malabsorption Syndromes ,Male ,Microvilli ,Mucolipidoses ,Mutation ,Myosin Heavy Chains ,Myosin Type V ,Pancreas ,Stomach ,Rab11a ,Myosin Vb ,MYO5B ,Syntaxin 3 ,Primary cilium ,Parietal cells ,BSEP ,Ezrin ,MRP2 ,Clinical Sciences ,Gastroenterology & Hepatology ,Clinical sciences - Abstract
ObjectivesMicrovillus inclusion disease (MVID) is a severe form of neonatal diarrhea, caused mainly by mutations in MYO5B. Inactivating mutations in MYO5B causes depolarization of enterocytes in the small intestine, which gives rise to chronic, unremitting secretory diarrhea. While the pathology of the small intestine in MVID patients is well described, little is known about extraintestinal effects of MYO5B mutation.MethodsWe examined stomach, liver, pancreas, colon, and kidney in Navajo MVID patients, who share a single homozygous MYO5B-P660L (1979C>T p.Pro660Leu, exon 16). Sections were stained for markers of the apical membrane to assess polarized trafficking.ResultsNavajo MVID patients showed notable changes in H/K-ATPase-containing tubulovesicle structure in the stomach parietal cells. Colonic mucosa was morphologically normal, but did show losses in apical ezrin and Syntaxin 3. Hepatocytes in the MVID patients displayed aberrant canalicular expression of the essential transporters MRP2 and BSEP. The pancreas showed small fragmented islets and a decrease in apical ezrin in pancreatic ducts. Kidney showed normal primary cilia.ConclusionsThese findings indicate that the effects of the P660L mutation in MYO5B in Navajo MVID patients are not limited to the small intestine, but that certain tissues may be able to compensate functionally for alterations in apical trafficking.
- Published
- 2018