Assessing the role of the ALS-associated gene NEK1 in zebrafish motor neuron development

Date
2017-04-11
Authors
Stark, Amy
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Altmetrics
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Genetics, Developmental and Cell Biology
Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease associated with the loss of motor neurons, ultimately leading to death of the patient. In recent years, a significant number of genes associated with the disease have been discovered, but it is still unknown how mutations in these genes can cause ALS. My project works with genome editing technology in the zebrafish, Danio rerio, to study the effect on motor neuron development and degeneration by producing knock-out and knock-in mutations in the fish. In particular, I am focusing my work on the NEK1 gene, a recently-discovered gene that could be linked to a significant number of ALS cases. I am using the CRISPR/Cas9 system to generate a loss-of-function allele for NEK1, which can induce a mutation to make a nonfunctional protein. Then, I can use this mutation in the zebrafish to analyze the role that the NEK1 gene plays in motor neuron development and degeneration, specifically related to ALS symptoms. Furthermore, in the future, I will test the isolated effect of the p.Arg261His amino acid substitution to understand its specific role in ALS cases, particularly whether this gene contributes in a dominant or recessive manner to causing the disease.

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