Muscular Dystrophic (<I>dy</I>) Mice: Bone-Muscle Imbalance Hypothesis

Abstract

Instead of “Muscle degeneration theory, ” we have previously proposed “Muscle defective maturation theory” and further “Bone-muscle imbalance hypothesis” in order to explain the pathogenesis of mouse muscular dystrophy. Consistent with this hypothesis, various interesting facts have been reported by many authors: 1. Dystrophic (dy) mice and dy chickens suffer from defective maturation of muscles. 2. A small stature or such treatments as cause a small stature, are beneficial to dy chickens, dy mice, Duchenne dy patients, dy hamsters and dy dogs. 3. The sarcomere of dy chicken muscle at the resting state is abnormally extended. 4. Passive stretch of adult chicken muscle produces a myopathy similar to muscular dystrophy. 5. A reduced load on muscles by immobilization, tenotomy, or suspension is beneficial to dy mice. 6. There is no direct correlation between the degrees in severity of muscle alterations and functional disabilities in forelegs of dy mice.In this report, we present some recent findings on muscular dystrophic mice (C57BL/6J-dy dy/dy) and discuss their pathological implications in connection with the bone-muscle imbalance hypothesis : 1. Pathological changes (central nucleation and fiber-size variation) did not seem to be the result of degeneration and impaired regeneration of muscle fibers. They have been assumed to be a reflex of defective maturation (growth) of fibers, a response of fibers to superordinary stretch, and/or the result of an injury-repair phenomenon which might occur locally along fibers on movement or even at the resting state with aggravation in bone-muscle imbalance. 2. Fibers of tongue and esophagus muscles, which were uninfluenced by the growth of bones, were microscopically normal. 3. Fibers of costal diaphragm muscles, which were arranged perpendicularly to bones, were apparently normal, as expected to be relatively less influenced by the growth of bones compared with those of limb muscles which were attached alongside to bones.