Analysis of ALS-associated genes in the zebrafish Danio rerio.
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2018-05
Authors
Smith, Courtney
Major Professor
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Trimarchi, Jeffrey
Committee Member
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Abstract
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the deterioration of the upper and lower motor neurons in the central nervous system. Although the pathogenesis of ALS is largely unknown, exome-sequencing studies have revealed new genes with mutations that are linked to familial or sporadic cases. The current challenge is to understand the in vivo function of these genes, with the hope that this insight will shed light on their connection to ALS pathology. The zebrafish is a great model organism to study this disease because its genome has been sequenced and is very similar to that of humans. To begin our investigation, we used in situ hybridization to visualize the expression of 21 genes throughout zebrafish development. Specifically, we focus on expression in the motor neurons, as these are the cells that die in ALS. Next, we have used clustered regulatory interspaced short palindromic repeats (CRISPRs) technology to engineer targeted mutations in a few of these ALS-linked genes in zebrafish. Ultimately, these experiments in zebrafish will provide insight into the role of these genes in motor neuron development and, we hope, ultimately point us toward a definitive link with ALS.
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