Drosophila RET Mutants as a Model for Hirschsprung's Disease

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Authors

Perera, Hiran

Issue Date

2016

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Thesis

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en_US

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Mutant RET protein can fail to activate neural migration pathways causing the newborn colon to lack neurons for peristalsis. Considered as Hirschsprung’s disease, no treatment exists to induce proper migration thus requiring resection of the non-innervated colon. Drosophila melanogaster’s RET is a close homolog to human RET. Fly RET mutants were characterized as possible models for Hirschsprung’s disease treatment testing. The mutants had five distinct characteristics relative to wild type: foraging behavior and decreased neuronal vesiculation, movement of gut food, larval growth, and survival time. The mutants were used to create a behavioral assay for treatment testing. Mutant Msn and GAP1 (RET phenotype enhancers) were tested as possible rescues but failed to better the RET mutant phenotype. The mutants’ problems in moving food, very similar to Hirschsprung’s disease patients that cannot move food past the colon, implies promise that the fly RET mutant can act as a model with five dimensions for treatment testing.

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