Dynein is a motor protein complex that transports various types of intracellular cargos from the cell periphery towards the cell center. Dynein mutations are linked to several neurodegenerative diseases, including Charcot-Marie-Tooth disease (CMT). A mouse model of CMT was generated with a knock-in H304R dynein allele. This mutation at position 304 corresponds to the H306R mutation found in humans that can cause CMT. Here, a behavioral test was developed to study the onset and progression of CMT symptoms in these mice. In the tail suspension test, mice were suspended briefly by their tails and the posture of their hind limbs was scored. Wildtype mice spread their hind limbs outwards in a characteristic splayed posture, whereas heterozygous and homozygous mutants display abnormal phenotypes. In further investigation, the neuromuscular junctions of these mice were analyzed in order to understand the histological effects of the mutation and how the potential differences could result in the behavioral effects observed. The extent of neuromuscular junction innervation was examined along with the size and complexity of the neuromuscular junctions themselves through multiple criteria. This, when combined with the effects observed during the tail suspension behavioral test, seeks to establish the H304R mutant mouse as a successful model for CMT.
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King, Stephen J.
Bachelor of Science (B.S.)
College of Medicine
Dissertations, Academic -- Medicine; Medicine -- Dissertations, Academic
Length of Campus-only Access
Honors in the Major Thesis
Ledray, Aaron, "Characterizing the Onset and Progression of Charcot-Marie-Tooth Neuropathy in H304R Mutant Mice" (2015). HIM 1990-2015. 1790.