Mice lacking the myotonic dystrophy protein kinase develop a late onset progressive myopathy.
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.
Reddy
S
S
Center for Cancer Research, M.I.T. Cambridge, Massachusetts 02138, USA.
Smith
D B
DB
Rich
M M
MM
Leferovich
J M
JM
Reilly
P
P
Davis
B M
BM
Tran
K
K
Rayburn
H
H
Bronson
R
R
Cros
D
D
Balice-Gordon
R J
RJ
Housman
D
D
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
C585517:DMPK protein, human; C585516:DMPK protein, mouse; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases