Thesis

The determination of muscle wasting and litter sizes in the M712T animal model

Hereditary Inclusion Body Myopathy (HIBM) is a homozygous recessive disorder characterized by the M712T mutation. Humans who inherit this disorder develop skeletal muscle wasting, which is largely attributed to a sialic acid deficiency. In order to develop a treatment for HIBM, a suitable animal model must be developed. Thus, my aim was to use the rotarod mechanism to determine if mice homozygous for the HIBM disorder developed a similar phenotype as humans. I also aimed to determine the differences in litter sizes between affected and normal mice. I used the rotarod treadmill to assess the muscular strength of three groups: mice homozygous, heterozygous, and wild-type for the mutant M712T allele. I also compared the litter sizes of both heterozygous and normal mice breeding pairs. To perform genotyping on the mice, I used polyacrilamide gel electrophoresis. I found that there were insignificant differences between the three groups regarding rotarod performance time. As a group, heterozygotes performed the worst (1.30 seconds), followed by homozygotes (1.37 seconds), and then wild-type mice (1.60 seconds). Also, the strain of the mice dictated the severity of the M712T mutation. Regarding litter sizes, normal mice had greater litter sizes than mice heterozygous for the M712T mutant allele. Either our rotarod machine is not an ideal indicator of animal strength, or mice with the M712T mutation do not exhibit the muscle-wasting phenotype. The experiment should be repeated with a larger sample size, and histology studies should be performed to confirm the presence of muscle wasting.

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