The Metabolism of Creatine-1-C14 by Mice With Hereditary Muscular Dystrophy*

Creatinuria, diminished urinary creatinine ex- cretion and low concentrations of creatine in skele- tal muscle are characteristic findings in progressive muscular dystrophy in man (1).These abnormalities of creatine metabolism are sometimes thought to be nonspecific changes secondary to a smaller muscle mass (2), but this has not been proven; and, because of the probable importance of phosphocreatine to energy metabolism in skele- tal muscle (3), it is possible that an abnormality of creatine metabolism would contribute to the weakness if not to the actual damage of muscle fibers in muscular dystrophy.It is therefore im- portant to establish the nature of the defect in creatine metabolism in muscular dystrophy.Since the hereditary myopathy of mice de- scribed by Michelson, Russell and Harman (4) resembles progressive muscular dystrophy, an in- vestigation of creatine metabolism in these mice was undertaken.It was found that the muscle creatine of the dystrophic mouse has a shortened turnover time1 which suggests that the low con- centration of creatine in the skeletal muscle in this condition is due to an impaired ability to retain creatine. METHODSStrain 129 dystrophic mice and their normal litter mates, approximately 8 weeks of age and of both sexes, were obtained from the Roscoe B. Jackson Memorial Laboratory.