The absence of dystrophic characteristics in normal muscles successfully cross-reinnervated by nerves of dystrophic genotype: Physiological and cytochemical study of crossed solei of normal and dystrophic parabiotic mice

Dystrophic mice and normal littermates were joined in parabiotic union between 20 to 23 days of age with a cross of the “fast” tibial nerve of one partner to the slow soleus muscle of the other. This preparation allowed us (a) to monitor the “neurotrophic” influences of “fast” nerves on slow muscles and (b) to assess the influence of these nerves on the expression of hereditary muscular dystrophy. Twelve parabiotic pairs examined 3 to 6 months postoperatively reveal that the cross-reinnervated solei, either normal or dystrophic, exhibit post-tetanic potentiation, a mean 30% decrease in contraction time, and a mean 48% decrease in half-relaxation time as compared to the contralateral control muscles which were self-reinnervated. Self-reinnervated dystrophic solei generate 60% less tension than do self-reinnervated normal solei. The contractile capabilities of solei of the dystrophic mice cross-reinnervated by nerves of the normal partners are not enhanced, nor are these parameters reduced in normal solei receiving nerves of dystrophic genotype. Instead, cross-reinnervated solei exhibit twitch and tetanic tensions similar to those of their contralateral control muscles. Cytochemical and structural analyses indicate that the crossed “fast” nerves of normal or of dystrophic genotype are effective in altering the cytochemical pattern of the slow muscles to fiber types characteristic of fast muscles. However, normal nerves innervating solei of the dystrophic parabiont do not arrest the progress of the disease, and nerves of dystrophic genotype innervating muscles of the normal parabiont do not induce a pathological state. The results indicate that the peripheral motor nerves of dystrophic mice are normal in exerting “neurotrophic” influences and that muscular dystrophy progresses in spite of the presence of normal “neurotrophic” influences. This unique approach of a double nerve cross achieved through parabiosis gives strong evidence that the etiology of hereditary muscular dystrophy in this species is not nerve mediated.