title: Mice lacking the myotonic dystrophy protein kinase develop a late onset progressive myopathy.
abstract: Myotonic dystrophy (DM) is an autosomal dominant disorder resulting from the expansion of a CTG repeat in the 3' untranslated region of a putative protein kinase (DMPK). To elucidate the role of DMPK in DM pathogenesis we have developed Dmpk deficient (Dmpk-/-) mice. Dmpk-/-mice develop a late-onset, progressive skeletal myopathy that shares some pathological features with DM. Muscles from mature mice show variation in fibre size, increased fibre degeneration and fibrosis. Adult Dmpk-/-mice show ultrastructural changes in muscle and a 50% decrease in force generation compared to young mice. Our results indicate that DMPK may be necessary for the maintenance of skeletal muscle structure and function and suggest that a decrease in DMPK levels may contribute to DM pathology.
authors.affiliation: Center for Cancer Research, M.I.T. Cambridge, Massachusetts 02138, USA.
authors.forename: S
authors.initials: S
authors.lastname: Reddy
authors.forename: D B
authors.initials: DB
authors.lastname: Smith
authors.forename: M M
authors.initials: MM
authors.lastname: Rich
authors.forename: J M
authors.initials: JM
authors.lastname: Leferovich
authors.forename: P
authors.initials: P
authors.lastname: Reilly
authors.forename: B M
authors.initials: BM
authors.lastname: Davis
authors.forename: K
authors.initials: K
authors.lastname: Tran
authors.forename: H
authors.initials: H
authors.lastname: Rayburn
authors.forename: R
authors.initials: R
authors.lastname: Bronson
authors.forename: D
authors.initials: D
authors.lastname: Cros
authors.forename: R J
authors.initials: RJ
authors.lastname: Balice-Gordon
authors.forename: D
authors.initials: D
authors.lastname: Housman
mesh_terms: D000818:Animals; D004576:Electromyography; D005260:Female; D006720:Homozygote; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018763:Muscle Fatigue; D018485:Muscle Fibers, Skeletal / Q000737:chemistry / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D009154:Mutation; D009223:Myotonic Dystrophy / Q000235:genetics / Q000473:pathology; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D012038:Regeneration
chemical_list: C585517:DMPK protein, human; C585516:DMPK protein, mouse; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases