An inducible mouse model for microvillus inclusion disease reveals a role for myosin Vb in apical and basolateral trafficking
Copyright policy )An inducible mouse model for microvillus inclusion disease reveals a role for myosin Vb in apical and basolateral trafficking
Significance Microvillus inclusion disease (MVID) is a rare intestinal enteropathy resulting in severe diarrhoea in neonates. Here, we have generated an intestine-specific knockout mouse model for Myosin Vb, the gene causing MVID in the majority of human patients. Our mouse model completely recapitulates the intestinal human MVID phenotype, including severe diarrhoea, loss of microvilli, occurrence of microvillus inclusions, and subapical secretory granules in villus enterocytes. In addition, we identify a newly identified role of Myo5b in trafficking of basolateral proteins, in the apical localization of the brush border membrane fusion protein syntaxin 3 (STX3), and in early differentiation of enterocytes. Our data indicate a role of MYO5B in regulating polarity of epithelial cells and have important implications for future treatment options for MVID patients.
- Utrecht University Netherlands
- University of Freiburg Germany
- Wilhelmina Children's Hospital Netherlands
- Boston Children's Hospital United States
- University Medical Center Freiburg Germany
Male, epithelila polarity, RECOMBINATION, Inbred C57BL, Transgenic, Mice, Mucolipidoses, Intestinal Mucosa, PHOSPHORYLATION, EZRIN, Mice, Knockout, Microscopy, Microscopy, Confocal, Microvilli, Research Support, Non-U.S. Gov't, EPITHELIAL-CELLS, Immunohistochemistry, Intestines, Protein Transport, DIFFERENTIATION, Confocal, Female, STEM-CELLS, myosin Vb, POLARITY, mouse model, Knockout, Myosin Type V, Mice, Transgenic, Electron, Organ Culture Techniques, SDG 3 - Good Health and Well-being, Malabsorption Syndromes, Microscopy, Electron, Transmission, Journal Article, Transmission, Animals, Humans, Animal, MYO5B MUTATIONS, Inbred CBA, Epithelial Cells, intestinal enteropathy, Mice, Inbred C57BL, MICE, Tamoxifen, Disease Models, Animal, Enterocytes, Disease Models, Mice, Inbred CBA, MEMBRANE, microvillus inclusion disease
Male, epithelila polarity, RECOMBINATION, Inbred C57BL, Transgenic, Mice, Mucolipidoses, Intestinal Mucosa, PHOSPHORYLATION, EZRIN, Mice, Knockout, Microscopy, Microscopy, Confocal, Microvilli, Research Support, Non-U.S. Gov't, EPITHELIAL-CELLS, Immunohistochemistry, Intestines, Protein Transport, DIFFERENTIATION, Confocal, Female, STEM-CELLS, myosin Vb, POLARITY, mouse model, Knockout, Myosin Type V, Mice, Transgenic, Electron, Organ Culture Techniques, SDG 3 - Good Health and Well-being, Malabsorption Syndromes, Microscopy, Electron, Transmission, Journal Article, Transmission, Animals, Humans, Animal, MYO5B MUTATIONS, Inbred CBA, Epithelial Cells, intestinal enteropathy, Mice, Inbred C57BL, MICE, Tamoxifen, Disease Models, Animal, Enterocytes, Disease Models, Mice, Inbred CBA, MEMBRANE, microvillus inclusion disease
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