Parabiotic reinnervation in normal and dystrophic mice. Part 2. Morphological studies

The technique of parabiotic reinnervation has been used to test directly the neurogenic theory of the aetiology of muscular dystrophy in mice. Dystrophic muscles contain significantly fewer muscle fibres than their normal controls; they also have a much broader spectrum of fibre size because of a much higher proportion of very small fibres and are poorly differentiated into histochemical fibre types. These criteria were used to assess whether there was any amelioration of the dystrophic process in response to the introduction of a normal nerve supply, or whether dystrophic changes were induced in normal muscle reinnervated with a dystrophic nerve. Self-reinnervated normal and dystrophic TA and EDL muscles contained the same numbers of fibres as unoperated controls. The process of parabiosis alone resulted in no changes in normal or dystrophic muscles. In the process of parabiotic reinnervation, the efficiency of the reinnervation process was not affected by the parabiotic state. The parabiotic reinnervation of dystrophic muscle by normal nerve resulted in no significant increase in fibre numbers and the spectrum of fibre sizes was essentially the same as in unoperated dystrophic muscle. The parabiotic reinnervation of normal muscle by dystrophic nerve resulted in a reduction of fibre numbers in only some of the muscles examined. However, the spectrum of fibre diameters remained essentially normal, and the differentiation of the fibres into histochemical fibre types was characteristic of reinnervated normal muscle. There was a marked absence of necrosis or of other histological signs of dystrophy in these muscles. Since there was no positive evidence to show that conversion of normal to dystrophic, or dystrophic to normal muscle occurred under the influence of parabiotic nerve transposition, two alternative conclusions were admissible. Firstly, the influence of dystrophic nerve upon muscle may be operative in fetal or neonatal life and may be irreversible by means of the subsequent introduction of a normal nerve supply. Secondly, the dystrophic state in muscle may be determined by genetic factors independent of nerve supply.