The mdx mouse model as a surrogate for Duchenne muscular dystrophy

Abstract

Research into fundamental principles and the testing of therapeutic hypotheses for treatment of human disease is commonly performed on mouse models of human diseases. Although this is often the only practicable approach, it carries a number of caveats arising from differences between the two species. This review focuses on the example of skeletal muscle disease, in particular muscular dystrophy, to identify some of the principal classes of obstacles to translation of data from mouse to humans. Of these, the difference in scale is one of the most commonly ignored, and is of particular interest because it has quite major repercussions for evaluation of some classes of intervention and of outcome criteria, while having comparatively little bearing on others. Likewise, inter-species differences and similarities in cell and molecular biological mechanisms underlying development, growth and response to pathological processes should be considered on an individual basis. An awareness of such distinctions is crucial if we are to avoid misjudging the likely applicability to humans of results obtained on mouse models.

Keywords: developmental differences; double mutants; effects of scale; growth differences; inter-species translation; lifespan; murine disease model; muscular dystrophy; pharmacological variation; preclinical research.