title: Myo5b knockout mice as a model of microvillus inclusion disease.
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.
authors.affiliation: 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.
authors.forename: Fernando
authors.initials: F
authors.lastname: Cartón-García
authors.affiliation: Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Arend W
authors.initials: AW
authors.lastname: Overeem
authors.affiliation: 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.
authors.forename: Rocio
authors.initials: R
authors.lastname: Nieto
authors.affiliation: 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.
authors.forename: Sarah
authors.initials: S
authors.lastname: Bazzocco
authors.affiliation: 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.
authors.forename: Higinio
authors.initials: H
authors.lastname: Dopeso
authors.affiliation: 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.
authors.forename: Irati
authors.initials: I
authors.lastname: Macaya
authors.affiliation: 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.
authors.forename: Josipa
authors.initials: J
authors.lastname: Bilic
authors.affiliation: Department of Pathology, Vall d'Hebron Hospital, Barcelona, Spain.
authors.forename: Stefania
authors.initials: S
authors.lastname: Landolfi
authors.affiliation: Department of Pathology, Vall d'Hebron Hospital, Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Hernandez-Losa
authors.affiliation: Group of Drug Delivery and Targeting, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Simo
authors.initials: S
authors.lastname: Schwartz
authors.affiliation: Department of Pathology, Vall d'Hebron Hospital, Barcelona, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Ramon y Cajal
authors.affiliation: Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Sven C D
authors.initials: SC
authors.lastname: van Ijzendoorn
authors.affiliation: 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.
authors.forename: Diego
authors.initials: D
authors.lastname: Arango
mesh_terms: D000818:Animals; D003967:Diarrhea / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D008286:Malabsorption Syndromes / Q000150:complications / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008871:Microvilli / Q000473:pathology*; D009081:Mucolipidoses / Q000150:complications / Q000473:pathology* / Q000503:physiopathology*; D024701:Myosin Type V / Q000235:genetics* / Q000378:metabolism
chemical_list: C588269:Myo5B protein, mouse; D024701:Myosin Type V