Experimental Manipulation Which Results in the Phenotypic Expression of the Dystrophic Process: Cross-reinnervation of a Slow Tonic Muscle by the Nerve of a Fast Twitch Muscle in Chickens With Hereditary Muscular Dystrophy
Date of Award
Doctor of Philosophy (PhD)
Professor Ethel Cosmos
In chickens afflicted with hereditary muscular dystrophy, the two major types of muscle present respond dissimilarly to the disease process: fast twitch glycolytic muscles possess and express the dystrophic gene overtly during ex ovo development while the genotypically dystrophic slow tonic muscles fail to express dystrophic phenotypes. Therefore, in chickens, muscular dystrophy is muscle fibre type specific.
The primary goal of this thesis was to experimentally alter the genetically dystrophic slow tonic musle in an attempt to induce this muscle to express dystrophic phenotypes. Since motor nerves influence the phenotypes of skeletal muscles, it was decided to replace the motor innervation of a slow tonic muscle with that of a fast twitch muscle within a-dystrophic chicken. The surgical cross-reinnervation between the ALD muscle and the 'fast' nerve was performed at hatching by transposing the right ALD muscle to the left side of the back in order to prevent selective self-reinnervation by the severed ALD nerve. The experimental muscles were examined at various time intervals from 2 to 104 weeks postoperatively and compared to age-matched ALD muscles in genetically normal chickens. In addition, denervation of ALD muscles, with and without transposition served as control experiments.
Selected histochemical and structural properties of unoperated ALD and fast twitch posterior latissimus dorsi (PLD) muscles of normal and dystrophic chickens were compared between 2 and 32 weeks ex ovo to provide criteria for the analysis of muscles cross-reinnervated by 'fast' nerves and to determine which of these parameters were altered as a result of the dystrophic process. Normal and dystrophic ALD muscles exhibited similar phenotypes: acid and alkaline stable myosin ATPase activity, 'en grappe' endplates, weak glycolytic and strong oxidative capacities, and peripheral location of nuclei. Furthermore, the growth rate, size, and shape of fibres in the normal and dystrophic ALD muscles were similar. In contrast, the myosin ATPase and innervation patterns of normal and dystrophic PLD muscles differed from those of ALD muscles: PLD fibres of either genotype exhibited alkaline stable, acid labile myosin ATPase activity and focal 'en plaque' innervation. Normal and dystrophic PLD muscles also exhibited different phenotypes: dystrophic muscles had a lower muscle weight, abnormal size, shape, and growth rate of fibres, increased number of scattered nuclei, add abnormal glycolytic and oxidative capacities.
The results presented from this work indicate that the genetically dystrophic ALD muscles respond differently to cross-reinnervation than do normal ALD muscles. The cross-reinnervated muscles in normal birds demonstrated all of the characteristics of an unoperated ALD muscle with the exception of the presence of isolated groups of fibres exhibiting a fast twitch type of myosin ATPase response. This result suggests that the principle response of normal ALD muscles to a foreign 'fast" nerve is one of resistance to alteration. In contrast, data from the experimental ALD muscles of dystrophic genotype support the conclusion that these muscles are dramatically remodelled after cross-reinnervation. An augmented regenerative response within the dystrophic muscles resulted in hyperplasia which, in turn, led to a complete restructuring of these muscles. Therefore, the present cross-reinnervation experiments demonstrate, for the first time, that a phenotypically normal muscle of dystrophic genotype can be induced to express a dystrophic characteristic: an augmented regenerative response after an experimentally-induced injury. It is important to note that the initial induction of this dystrophic phenotype was demonstrated in the absence of the foreign 'fast' nerve and seemed to be due to the response of this muscle to the severe injury imposed upon the muscle during the inital operation.
Gandy, Alan Clarke, "Experimental Manipulation Which Results in the Phenotypic Expression of the Dystrophic Process: Cross-reinnervation of a Slow Tonic Muscle by the Nerve of a Fast Twitch Muscle in Chickens With Hereditary Muscular Dystrophy" (1985). Open Access Dissertations and Theses. Paper 1076.