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Updated: Feb 17, 2026
Immuno-fluorescent Labeling of Microtubules and Centrosomal Proteins in Ex Vivo Intestinal Tissue and 3D In Vitro Intestinal Organoids
Published on: December 13, 2017
Apical Membrane Alterations in Non-intestinal Organs in Microvillus Inclusion Disease
Cameron Schlegel1,2, Victoria G Weis1,2, Byron C Knowles3,2
1Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN, USA.
Objectives:
Microvillus 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.
Methods:
We 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.
Results:
Navajo 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.
Conclusions:
These 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.
Insights
Microvillus inclusion disease (MVID) caused by MYO5B mutations affects more than the small intestine. Extra-intestinal tissues like the stomach and liver show altered apical trafficking, though some tissues compensate.
Area of Science:
- Gastroenterology
- Cell Biology
- Genetics
Background:
- Microvillus inclusion disease (MVID) is a severe neonatal diarrhea primarily caused by MYO5B mutations.
- MYO5B mutations lead to enterocyte depolarization and chronic secretory diarrhea, with small intestine pathology well-documented.
- Extraintestinal manifestations of MYO5B mutations remain largely unexplored.
Purpose of the Study:
- To investigate the extraintestinal effects of a specific MYO5B mutation (P660L) in Navajo MVID patients.
- To assess polarized trafficking in various organs beyond the small intestine.
Main Methods:
- Examination of stomach, liver, pancreas, colon, and kidney tissues from Navajo MVID patients with a homozygous MYO5B-P660L mutation.
- Staining tissue sections for apical membrane markers to evaluate polarized trafficking.
Main Results:
- Stomach parietal cells exhibited altered H/K-ATPase tubulovesicle structure.
- Colonic mucosa showed reduced apical ezrin and Syntaxin 3, despite normal morphology.
- Hepatocytes displayed aberrant expression of MRP2 and BSEP transporters.
- Pancreatic islets were smaller and fragmented, with decreased apical ezrin in ducts.
- Kidney primary cilia appeared normal.
Conclusions:
- The P660L MYO5B mutation's effects extend beyond the small intestine.
- Specific tissues demonstrate functional compensation for disrupted apical trafficking.
- This study highlights the systemic impact of MYO5B mutations in MVID.
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