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ZIRC
ZFIN ID: ZDB-PUB-160809-11
The zebrafish goosepimples/myosin Vb mutant exhibits cellular attributes of human microvillus inclusion disease
Sidhaye, J., Pinto, C.S., Dharap, S., Jacob, T., Bhargava, S., Sonawane, M.
Date: 2016
Source: Mechanisms of Development   142: 62-74 (Journal)
Registered Authors: Jacob, Tressa Panikulangara, Sidhaye, Jaydeep, Sonawane, Mahendra
Keywords: Disease model, Gut morphogenesis, Intestine, Microvillus inclusion disease, Zebrafish
MeSH Terms:
  • Animals
  • Disease Models, Animal
  • Humans
  • Intestine, Small/physiopathology*
  • Malabsorption Syndromes/genetics*
  • Malabsorption Syndromes/physiopathology
  • Microvilli/genetics
  • Microvilli/pathology*
  • Mucolipidoses/genetics*
  • Mucolipidoses/physiopathology
  • Mutant Proteins/genetics*
  • Mutation
  • Myosin Heavy Chains/genetics*
  • Myosin Type V/genetics*
  • Zebrafish/genetics
  • Zebrafish/physiology
PubMed: 27497746 Full text @ Mech. Dev.
FIGURES
ABSTRACT
Microvillus inclusion disease (MVID) is a life threatening enteropathy characterised by malabsorption and incapacitating fluid loss due to chronic diarrhoea. Histological analysis has revealed that enterocytes in MVID patients exhibit reduction of microvilli, presence of microvillus inclusion bodies and intestinal villus atrophy, whereas genetic linkage analysis has identified mutations in myosin Vb gene as the main cause of MVID.In order to understand the cellular basis of MVID and the associated formation of inclusion bodies, an animal model that develops ex-utero and is tractable genetically as well as by microscopy would be highly useful. Here we report that the intestine of the zebrafish goosepimples (gsp)/myosin Vb (myoVb) mutant shows severe reduction in the intestinal folds- structures similar to mammalian villi. The loss of folds is further correlated with changes in the shape of enterocytes. In a striking similarity with MVID patients, zebrafish gsp/myoVb mutant larvae exhibit microvillus atrophy, microvillus inclusions and accumulation of secretory material in enterocytes. We propose that the zebrafish gsp/myoVb mutant is a valuable model to study the pathophysiology of MVID. Furthermore, owing to the advantages of zebrafish in screening libraries of small molecules, the gsp mutant will be an ideal tool to identify compounds having therapeutic value against MVID.
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