EFFECT OF PROPYLTHIOURACIL-INDUCED HYPOTHYROIDISM ON THE ONSET OF SKELETAL-MUSCLE NECROSIS IN DYSTROPHIN-DEFICIENT MDX MICE

1. Duchenne and Becker muscular dystrophies are X-lin ked disorders ca used by defects in muscle dystrophin. The mdx mouse is an animal model for Duchenne muscular dystrophy which has a point mutation in the dys trophin gene, resulting in little (< 3 %) or no expression of dystroph in in muscle. Mdx mice show a characteristic pattern of muscle necrosi s and regeneration. Muscles are normal until the third postnatal week when widespread necrosis commences. This is followed by muscle regener ation, with the persistence of centrally nucleated fibres. 2. This wor k has examined the hypothesis that the onset of this muscle necrosis i s associated with postnatal maturation of the thyroid endocrine system and that pharmacological inhibition of thyroid hormone synthesis dela ys the onset of muscle necrosis. 3. Serum T-4 and T-3 concentrations o f mice were found to rise immediately before the onset of muscle necro sis in the mdx mouse, and induction of hypothyroidism by treatment of animals with propylthiouracil was found to delay the onset of muscle n ecrosis. 4. The results provide the first demonstration of experimenta l delay of muscle necrosis by manipulation of the endocrine system in muscle lacking dystrophin, and provide a novel insight into the way in which a lack of dystrophin interacts with postnatal development to pr ecipitate muscle necrosis in the mdx mouse.