Mice lacking the myotonic dystrophy protein kinase develop a late onset progressive myopathy

Sita Reddy; Daniel B.J. Smith; Mark M. Rich; John M. Leferovich; Patricia Reilly; Brigid M. Davis; Khoa Tran; Helen Rayburn; Roderick Bronson; Didier Cros; Rita J. Balice-Gordon; David Housman

doi:10.1038/ng0796-325

Mice lacking the myotonic dystrophy protein kinase develop a late onset progressive myopathy

Sita Reddy, Daniel B.J. Smith, Mark M. Rich, John M. Leferovich, Patricia Reilly, Brigid M. Davis, Khoa Tran, Helen Rayburn, Roderick Bronson, Didier Cros, Rita J. Balice-Gordon, David Housman

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293 Scopus citations

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.

Original language	English
Pages (from-to)	325-335
Number of pages	11
Journal	Nature Genetics
Volume	13
Issue number	3
DOIs	https://doi.org/10.1038/ng0796-325
State	Published - Jul 1996
Externally published	Yes

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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.",

author = "Sita Reddy and Smith, {Daniel B.J.} and Rich, {Mark M.} and Leferovich, {John M.} and Patricia Reilly and Davis, {Brigid M.} and Khoa Tran and Helen Rayburn and Roderick Bronson and Didier Cros and Balice-Gordon, {Rita J.} and David Housman",

year = "1996",

month = jul,

doi = "10.1038/ng0796-325",

language = "English",

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pages = "325--335",

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TY - JOUR

T1 - Mice lacking the myotonic dystrophy protein kinase develop a late onset progressive myopathy

AU - Reddy, Sita

AU - Smith, Daniel B.J.

AU - Rich, Mark M.

AU - Leferovich, John M.

AU - Reilly, Patricia

AU - Davis, Brigid M.

AU - Tran, Khoa

AU - Rayburn, Helen

AU - Bronson, Roderick

AU - Cros, Didier

AU - Balice-Gordon, Rita J.

AU - Housman, David

PY - 1996/7

Y1 - 1996/7

N2 - 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.

AB - 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.

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Mice lacking the myotonic dystrophy protein kinase develop a late onset progressive myopathy

Abstract

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