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Sci Rep. 2015 Jul 23;5:12312. doi: 10.1038/srep12312.

Myo5b knockout mice as a model of microvillus inclusion disease.

Author information

1
1] 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.
2
Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
3
Department of Pathology, Vall d'Hebron Hospital, Barcelona, Spain.
4
Group of Drug Delivery and Targeting, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, 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.

PMID:
26201991
PMCID:
PMC4511872
DOI:
10.1038/srep12312
[Indexed for MEDLINE]
Free PMC Article

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