The effects of muscular dystrophy on craniofacial growth in mice: A study of heterochrony and ontogenetic allometry

Mechanical loading of muscles on bones at their sites of attachment can regulate skeletal morphology. The present study examined the effects of muscle degeneration on craniofacial growth, using two strains of muscular dystrophic mice, Mus musculus, differing in pathological severity. We collected radiographic and weight data longitudinally and digitized radiographs to obtain distances between anatomical landmarks in different functional regions of the skull. We then quantified heterochronic and allometric differences among genotypes and between sexes. Because growth is nonlinear with respect to time, we first used the Gompertz model to obtain heterochronic growth parameters, which were then tested with ANOVA. Ontogenetic allometric analyses examined the scaling relationships between various measurements with linear regressions. For most measurements the severely dystrophic mice are significantly smaller in final size than both the control and the mildly dystrophic mice, which are statistically indistinguishable. Measures of total growth and the neurocranium exhibit more differences among groups in heterochronic parameters of early ontogeny because growth in these regions is controlled primarily by brain expansion that ceases early in development. In contrast, the face and mandible exhibit more differences in later growth parameters possibly because of the increased influence of muscles on these regions as growth progresses. The severely dystrophic mice have flatter, more elongate skulls and mandibles than those of the other two genotypes, concurrent with an absence of muscular forces to stimulate growth in a superior-inferior direction.