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.
","abstract_html":"<p>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.</p>","abstract_has_math":false,"creators":["Cowley, Patrick Michael"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation","degree_discipline":"Exercise Science","degree_department":null,"school":null,"contributors":["Keith C. DeRuisseau"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2011,"date_issued":"2011-12-01T08:00:00Z","date_published":"2011-12-01T08:00:00Z","updated_at":"2026-07-24T04:54:02Z","subjects":["Antioxidants","Down syndrome","Microarray","Muscle Contraction","Muscle Strength","Oxidative Stress","Kinesiology"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://surface.syr.edu/ppe_etd/5","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Keith C. DeRuisseau"]},{"key":"dc:creator","label":"Author","values":["Cowley, Patrick Michael"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"thesis:degree_discipline","label":"Discipline","values":["Exercise Science"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Antioxidants","Down syndrome","Microarray","Muscle Contraction","Muscle Strength","Oxidative Stress","Kinesiology"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://surface.syr.edu/ppe_etd/5"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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.
"]},{"key":"dc:title","label":"Title","values":["Skeletal Muscle Function, Morphology, and Biochemistry in Ts65Dn Mice: A Model of Down Syndrome"]}]}],"canonical_facts":{"dc:contributor":["Keith C. DeRuisseau"],"dc:creator":["Cowley, Patrick Michael"],"dc:description.abstract":["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.
"],"dc:identifier":["https://surface.syr.edu/ppe_etd/5"],"dc:subject":["Antioxidants","Down syndrome","Microarray","Muscle Contraction","Muscle Strength","Oxidative Stress","Kinesiology"],"dc:title":["Skeletal Muscle Function, Morphology, and Biochemistry in Ts65Dn Mice: A Model of Down Syndrome"],"thesis:degree_discipline":["Exercise Science"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T04:54:02Z"}