Three mouse models of muscular dystrophy: the natural history of strength and fatigue in dystrophin-, dystrophin/utrophin-, and laminin alpha 2-deficient mice

To optimize and evaluate treatments for muscular dystrophy, it is important to know the natural history of the disease in the absence of therapeutic i ntervention. Here we characterized disease progression of three mutant mous e strains of muscular dystrophy: mdx mice, which lack dystrophin mdx:utrn-/ - mice, which also lack utrophin and dy/dy mice, which are deficient in lam inin alpha2. Normal mice show a marked increase in forelimb strength over t he first 10 weeks of life and little fatigue (<5%) over five consecutive st rength trials. Mdx and mdx:utrn-/- mice demonstrate less strength then norm al mice and approximately 40% fatigue at each age. Mdx mice become obese bu t mdx:utrn-/- mice do not. Dy/dy mice remain small and are much weaker than mdx and mdx:utrn-/- mice at all ages even when normalized to weight; howev er, they show only minimal fatigue ( MIT). This work demonstrates a distinc t pattern of disease progression in each model and provides a foundation fo r assessing strategies for improving strength in each model. (C) 2001 Elsev ier Science B.V. All rights reserved.