Myo5b knockout mice as a model of microvillus inclusion disease
| Autor: | Cartón-Garcia, Fernando, Overeem, Arend W., Nieto Raya, Rocio, Bazzocco, Sarah, Dopeso, Higinio, Macaya, Irati, Bilic Zimmermann, Josipa, Landolfi, Stefania, Hernandez-Losa, Javier, Schwartz, Simo, Ramon y Cajal, Santiago, van Ijzendoorn, Sven C. D., Arango, Diego, Universitat Autònoma de Barcelona |
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| Přispěvatelé: | Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Center for Liver, Digestive and Metabolic Diseases (CLDM) |
| Rok vydání: | 2015 |
| Předmět: |
Diarrhea
Male EXPRESSION Pathology medicine.medical_specialty RAB8A Myosin Type V GENE-FUNCTION Biology Article ATROPHY Inclusion bodies Mice Atrophy Malabsorption Syndromes Mucolipidoses medicine Animals Epithelial polarity Mice Knockout Multidisciplinary Microvilli MUTATIONS MYOSIN VB Basolateral plasma membrane medicine.disease Microvillus Phenotype STEM-CELL Mice Inbred C57BL Disease Models Animal DIFFERENTIATION medicine.anatomical_structure Knockout mouse EPITHELIAL-CELL POLARITY Female Stem cell SKIN |
| Zdroj: | Scientific Reports, 5:12312. Nature Publishing Group Scientific Reports Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep12312 |
| Popis: | Inherited MYO5B mutations have recently been associated with microvillus inclusion disease (MVID), an autosomal recessive syndrome characterized by intractable, life-threatening, watery diarrhea appearing shortly after birth. Characterization of the molecular mechanisms underlying this disease and development of novel therapeutic approaches is hampered by the lack of animal models. In this study we describe the phenotype of a novel mouse model with targeted inactivation of Myo5b. Myo5b knockout mice show perinatal mortality, diarrhea and the characteristic mislocalization of apical and basolateral plasma membrane markers in enterocytes. Moreover, in transmission electron preparations, we observed microvillus atrophy and the presence of microvillus inclusion bodies. Importantly, Myo5b knockout embryos at day 20 of gestation already display all these structural defects, indicating that they are tissue autonomous rather than secondary to environmental cues, such as the long-term absence of nutrients in the intestine. Myo5b knockout mice closely resemble the phenotype of MVID patients and constitute a useful model to further investigate the underlying molecular mechanism of this disease and to preclinically assess the efficacy of novel therapeutic approaches. |
| Databáze: | OpenAIRE |
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