title: Three mouse models of muscular dystrophy: the natural history of strength and fatigue in dystrophin-, dystrophin/utrophin-, and laminin alpha2-deficient mice.
abstract: To optimize and evaluate treatments for muscular dystrophy, it is important to know the natural history of the disease in the absence of therapeutic intervention. Here we characterized disease progression of three mutant mouse strains of muscular dystrophy: mdx mice, which lack dystrophin; mdx:utrn-/- mice, which also lack utrophin; and dy/dy mice, which are deficient in laminin alpha2. Normal mice show a marked increase in forelimb strength over the first 10 weeks of life and little fatigue (<5%) over five consecutive strength trials. Mdx and mdx:utrn-/- mice demonstrate less strength then normal mice and approximately 40% fatigue at each age. Mdx mice become obese but 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; however, they show only minimal fatigue (10%). This work demonstrates a distinct pattern of disease progression in each model and provides a foundation for assessing strategies for improving strength in each model.
authors.affiliation: Department of Neurology, Washington University School of Medicine, Box 8111 660 S. Euclid, Saint Louis, MO 63110, USA. connolly@kids.wustl.edu
authors.forename: A M
authors.initials: AM
authors.lastname: Connolly
authors.forename: R M
authors.initials: RM
authors.lastname: Keeling
authors.forename: S
authors.initials: S
authors.lastname: Mehta
authors.forename: A
authors.initials: A
authors.lastname: Pestronk
authors.forename: J R
authors.initials: JR
authors.lastname: Sanes
mesh_terms: D000375:Aging; D000818:Animals; D001835:Body Weight; D003598:Cytoskeletal Proteins / Q000172:deficiency* / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D016189:Dystrophin / Q000172:deficiency* / Q000235:genetics; D005221:Fatigue / Q000209:etiology / Q000503:physiopathology; D005552:Forelimb / Q000473:pathology / Q000503:physiopathology; D018737:Hand Strength; D007797:Laminin / Q000172:deficiency* / Q000235:genetics; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D018101:Mice, Inbred mdx; D008817:Mice, Mutant Strains; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology; D009137:Muscular Dystrophy, Animal / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D009765:Obesity / Q000150:complications; D015996:Survival Rate; D049411:Utrophin
chemical_list: D003598:Cytoskeletal Proteins; D016189:Dystrophin; D007797:Laminin; D008565:Membrane Proteins; C483600:Utrn protein, mouse; D049411:Utrophin; C102645:laminin alpha 2