Home > Articles > Published articles > Myo5b knockout mice as a model of microvillus inclusion disease |
Date: | 2015 |
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. |
Grants: | Ministerio de Sanidad y Consumo CP05/00256 Ministerio de Economía, Industria y Competitividad TRA2009-0093 Ministerio de Ciencia e Innovación SAF2008-00789 Ministerio de Economía, Industria y Competitividad PI12/03103 Ministerio de Economía, Industria y Competitividad PI12/01095 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014FI_B00426 |
Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
Language: | Anglès |
Document: | Article ; recerca ; Versió publicada |
Published in: | Scientific reports, Vol. 5 (07 2015) , ISSN 2045-2322 |
10 p, 2.5 MB |