The Impact of Muscular Dystrophy on Limb Bone Growth and Scaling in Mice

Abstract

Muscular loading affects bone growth and the factors determining size and shape. However, it is not known what epigenetic impact muscular dystrophy (dystrophia muscularis) has on limb bone growth or ontogenetic scaling. To assess the effects of two types of muscular dystrophy (genotypes dy/dy and dy^2J/dy^2J) on limb bone growth, we measured lengths and widths of the right humerus, femur and tibia, and lengths of the ulna and radius from dorsal/ventral radiographs of mice taken over a period of 270 days. Radiographs were taken approximately 3 times a week, and the sampling frequency was gradually reduced to once a month. We plotted measurements from each individual against time and fit a Gompertz equation to the growth of each bone. Parameters of the equation were compared using ANOVA across genotypes and between sexes. Slopes of length versus width were calculated for the limb bones of each individual using linear regression. Slope differences among genotypes and between sexes were tested using ANOVA. Control and dy^2J values were significantly longer than those of dy mice in all bones, but there was considerable variation across genotypes for the various width measurements. Sexual dimorphism was found in several measurements, where males were always larger than females. There were few significant differences in limb scaling (lengths vs. widths) among genotypes and almost no scaling differences between sexes despite the size differences. Differences among widths suggest that muscular dystrophy affects different parts of limb bones in different ways. This may be the effect of the type and number of muscular attachments, as well as the usage of the limb. The sexually dimorphic measurements suggest that there are size differences in the skeleton between sexes, regardless of the genotype. Our ontogenetic allometry results indicate that size is affected by the muscular dystrophic condition and by sexual dimorphism, while shape remains largely unchanged.