Date of Award

2026-08-01

Degree Name

Master of Science

Department

Biological Sciences

Advisor(s)

Kendal D. Hirschi

Abstract

Missense mutations in the HCFC1 gene cause methymalonic acidemia with homocystinuria cblX type (MIM#309541). cblX is an X-linked disorder that is associated with multiple phenotypes such as metabolic defects, failure to thrive, intractable epilepsy, facial dysmorphia, movement disorders, and intellectual disability. The mechanisms underlying these phenotypes are not completely understood. Here we used a zebrafish germline mutant allele (hcfc1aco64/co64) to study seizure susceptibility and adult brain structural malformations. Previous studies have established neural progenitor cell defects and hypoactive mechanistic target of rapamycin (mTOR) in this allele. Given the known role of mTOR in seizure phenotypes, we hypothesized that missense mutation of zebrafish hcfc1a would alter seizure response to the established seizure inducing agent, pentylenetetrazol. Seizure was monitored through locomotor response. Mutation of hcfc1a did not elicit an increased seizure like response. Adult brain development was synergistically analyzed using hematoxylin and eosin stain. We identified abnormal morphology across brain regions, but variable expressivity in mutant animals. Future studies are warranted.

Language

en

Provenance

Received from ProQuest

File Size

51 p.

File Format

application/pdf

Rights Holder

Jose Manuel Fabela

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Biology Commons

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