Related Experiment Video
Updated: Apr 6, 2026
Modeling Charcot-Marie-Tooth Disease In Vitro by Transfecting Mouse Primary Motoneurons
Published on: January 7, 2019
Myo5b knockout mice as a model of microvillus inclusion disease
Fernando Cartón-García1, Arend W Overeem2, Rocio Nieto1
11] Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain [2] CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza, Spain.
Abstract:
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.
Insights
A new mouse model with Myo5b gene knockout mimics microvillus inclusion disease (MVID), exhibiting diarrhea and intestinal defects. This model is crucial for understanding MVID molecular mechanisms and testing new therapies.
Area of Science:
- Genetics and Molecular Biology
- Developmental Biology
- Gastroenterology
Background:
- Microvillus inclusion disease (MVID) is a severe congenital diarrheal disorder.
- Inherited MYO5B mutations are linked to MVID, but a lack of animal models hinders research.
- Understanding MVID pathogenesis requires a suitable preclinical model.
Purpose of the Study:
- To create and characterize a novel mouse model for MVID.
- To investigate the role of Myo5b in intestinal development and function.
- To establish a platform for preclinical therapeutic testing in MVID.
Main Methods:
- Targeted inactivation of the Myo5b gene in mice.
- Phenotypic analysis of Myo5b knockout mice, including perinatal viability and diarrhea.
- Transmission electron microscopy to examine enterocyte ultrastructure.
- Assessment of plasma membrane marker localization in enterocytes.
Main Results:
- Myo5b knockout mice exhibit perinatal mortality and severe diarrhea.
- Characteristic mislocalization of apical and basolateral plasma membrane markers in enterocytes was observed.
- Microvillus atrophy and inclusion bodies were identified in the enterocytes of knockout mice.
- These structural defects were present in embryonic stages, indicating tissue autonomy.
Conclusions:
- Myo5b knockout mice accurately recapitulate the key features of human MVID.
- This mouse model provides a valuable tool for studying MVID molecular mechanisms.
- The model is suitable for preclinical evaluation of novel therapeutic strategies for MVID.
More Related Videos
Related Concept Videos
01:16In-vitro Mutagenesis
00:55Microvilli
These microvilli are predominantly present in cells lining the small intestine, kidney tubules, and certain cells in the respiratory and reproductive systems. By significantly expanding the surface area of the cell membrane, microvilli enhance the cell's capacity...