# The zebrafish goosepimples/myosin Vb mutant exhibits cellular attributes of human microvillus inclusion disease

## TL;DR

A zebrafish mutant with a myosin Vb gene defect shows intestinal features similar to a severe human digestive disease called microvillus inclusion disease.

## Contribution

The zebrafish goosepimples/myosin Vb mutant is proposed as a novel model for studying microvillus inclusion disease pathophysiology and drug screening.

## Key findings

- The zebrafish gsp/myoVb mutant shows intestinal fold reduction and enterocyte shape changes.
- The mutant exhibits microvillus atrophy, inclusions, and secretory material accumulation like in MVID patients.
- The model is suitable for screening small molecules to identify potential therapies for MVID.

## Abstract

Microvillus inclusion disease (MVID) is a life threatening enteropathy characterised by perpetual diarrhoea. Recent analysis has revealed that enterocytes in MVID patients exhibit reduction of microvilli, presence of microvillus inclusion bodies and intestinal villus atrophy. Genetic linkage analysis has identified mutations in myosin Vb gene as the main cause of MVID. An animal model that develops ex-utero and is tractable genetically as well as by microscopy would be highly useful to study the cellular basis of the formation of inclusion bodies.

Here we report that the intestine of the zebrafish goosepimples (gsp)/myosin Vb (myoVb) mutant show 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. Owing to the advantages of zebrafish in screening libraries of small molecules, the gsp mutant will be an appropriate tool to identify compounds that would alleviate the formation of microvillus inclusions and have therapeutic value.