“P MRS studies of skeletal muscle energetics and ionic balance in a new mouse model of Duchenne muscular dystrophy

Introduction “P MRS studies of skeletal muscle in patients with Duchenne muscular dystrophy (DMD. in which the sarcolemmal protein dystrophin is absent) and Becker muscular dystrophy (BMD. in which dystrophin is abnormal in structure and/or reduced in content) have consistently shown abnormalities in pH and metabolite concentration ratios.“’ In l:wo and ,n IY~BO studies have shown abnormalities of ionic regulation and homeostasis. but alterations in bioenergetics in vwo have not been proven conclusively. The mdx mouse also lacks dystrophin and has been widely studied as a model of DMD.’ Although it exhibits some of the pH and other metabolic markers of DMD. the mds mouse displays little pathophysiology. This may’ be associated with the upregulation of utrophin. a protein closely related to dystrophin and concentrated at the neuromuscular Junction. A new mouse model, the ‘double knockout’ (dko). which lacks both of the sarcolemmal proteins dystrophin and utrophin has recently been developed.’ It shows the progressive muscle vcastmg. cardiomyopathy and reduced life expectancy which characterise DMD. We have carried out “I’ MRS studies on dko mouse muscle in order to assess its suitability as a model of the human disease. Here we present our initial findings of a comparison between mdx. dko and control mice.