title: Dystrophin-deficient mdx mice display a reduced life span and are susceptible to spontaneous rhabdomyosarcoma.
abstract: Duchenne muscular dystrophy (DMD) is the most common, lethal genetic disorder of children. A number of animal models of muscular dystrophy exist, but the most effective model for characterizing the structural and functional properties of dystrophin and therapeutic interventions has been the mdx mouse. Despite the approximately 20 years of investigations of the mdx mouse, the impact of the disease on the life span of mdx mice and the cause of death remain unresolved. Consequently, a life span study of the mdx mouse was designed that included cohorts of male and female mdx and wild-type C57BL/10 mice housed under specific pathogen-free conditions with deaths restricted to natural causes and with examination of the carcasses for pathology. Compared with wild-type mice, both mdx male and female mice had reduced life spans and displayed a progressively dystrophic muscle histopathology. Surprisingly, old mdx mice were prone to develop muscle tumors that resembled the human form of alveolar rhabdomyosarcoma, a cancer associated with poor prognosis. Rhabdomyosarcomas have not been observed previously in nontransgenic mice. The results substantiate the mdx mouse as an important model system for studies of the pathogenesis of and potential remedies for DMD.
authors.affiliation: Department of Neurology, K243b HSB, Box 357720, 1959 N.E. Pacific St., University of Washington School of Medicine, Seattle, WA 98195-7720, USA. jsc5@u.washington.edu
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Chamberlain
authors.forename: Joseph
authors.initials: J
authors.lastname: Metzger
authors.forename: Morayma
authors.initials: M
authors.lastname: Reyes
authors.forename: DeWayne
authors.initials: D
authors.lastname: Townsend
authors.forename: John A
authors.initials: JA
authors.lastname: Faulkner
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics; D003964:Diaphragm / Q000473:pathology; D005121:Extremities; D005260:Female; D020022:Genetic Predisposition to Disease; D006394:Hemangiosarcoma / Q000235:genetics; D008136:Longevity / Q000235:genetics*; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx / Q000235:genetics / Q000502:physiology*; D019042:Muscle Neoplasms / Q000235:genetics* / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D012516:Osteosarcoma / Q000235:genetics; D018232:Rhabdomyosarcoma, Alveolar / Q000235:genetics* / Q000473:pathology; D013047:Specific Pathogen-Free Organisms; D014059:Tongue / Q000473:pathology