Overexpression of minibrain as a model of Down syndrome in Drosophila melanogaster

Mawhinney, Rebecca M. S. (Rebecca Mairin Skye) (2011) Overexpression of minibrain as a model of Down syndrome in Drosophila melanogaster. Masters thesis, Memorial University of Newfoundland.

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Abstract

Down Syndrome (DS) occurs in about one in every 700 human live births, and includes cognitive impairment, learning and memory deficits, and reductions in neuronal number, volume, and density. One major DS candidate gene, dual-specific tyrosine-regulated kinase la (dyrkla), encodes a protein that phosphorylates a variety of substrates. The Drosophila melanogaster homologue, minibrain (mnb), shares high sequence homology with human dyrkla and both are important in neural development. Here directed mnb overexpression was accomplished in flies using the UAS-GAL4 system of gene expression. Overall eye development and bristle density were affected when mnb was overexpressed ubiquitously and in neural tissues. Climbing ability was poor in flies ubiquitously overexpressing mnb, whereas precocious loss of climbing ability was observed in flies with neural mnb overexpression. Increased mnb shortened the lifespan and delayed eclosion. Altered mnb expression also affected survival on starvation media, suggesting a role for mnb in cell survival. Taken together, these phenotypes suggest mnb overexpression models aspects of Down Syndrome in fruit flies.

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