Date of Award
Doctor of Philosophy (PhD)
Keith C. DeRuisseau
Antioxidants, Down syndrome, Microarray, Muscle Contraction, Muscle Strength, Oxidative Stress
A common clinical observation of persons with Down syndrome at all developmental stages is hypotonia and generalized muscle weakness. The cause of muscle weakness in Down syndrome is not known and there is an immediate need to establish an acceptable animal model to explore the muscle dysfunction that is widely reported in the human population. Using a combination of functional, histological, and biochemical analyses this dissertation provides the initial characterization of skeletal muscle from the Ts65Dn mouse, a model of Down syndrome. The experiments revealed that Ts65Dn muscle over-expresses SOD1 protein but this did not lead to oxidative stress. Ts65Dn soleus muscles displayed normal force generation in the unfatigued state, but exhibited muscle weakness following fatiguing contractions. We show that a reduction in cytochrome c oxidase expression may contribute to the impaired muscle performance in Ts65Dn soleus. These findings support the use of the Ts65Dn mouse model of Down syndrome to delineate mechanisms of muscle dysfunction in the human condition.
Cowley, Patrick Michael, "Skeletal Muscle Function, Morphology, and Biochemistry in Ts65Dn Mice: A Model of Down Syndrome" (2011). Exercise Science - Dissertations. 5.