title: Abnormal myotonic dystrophy protein kinase levels produce only mild myopathy in mice.
abstract: Myotonic dystrophy (DM) is commonly associated with CTG repeat expansions within the gene for DM-protein kinase (DMPK). The effect of altered expression levels of DMPK, which is ubiquitously expressed in all muscle cell lineages during development, was examined by disrupting the endogenous Dmpk gene and overexpressing a normal human DMPK transgene in mice. Nullizygous (-/-) mice showed only inconsistent and minor size changes in head and neck muscle fibres at older age, animals with the highest DMPK transgene expression showed hypertrophic cardiomyopathy and enhanced neonatal mortality. However, both models lack other frequent DM symptoms including the fibre-type dependent atrophy, myotonia, cataract and male-infertility. These results strengthen the contention that simple loss- or gain-of-expression of DMPK is not the only crucial requirement for development of the disease.
authors.affiliation: Department of Cell Biology and Histology, Medical Faculty, University of Nijmegen, The Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: Jansen
authors.forename: P J
authors.initials: PJ
authors.lastname: Groenen
authors.forename: D
authors.initials: D
authors.lastname: Bächner
authors.forename: P H
authors.initials: PH
authors.lastname: Jap
authors.forename: M
authors.initials: M
authors.lastname: Coerwinkel
authors.forename: F
authors.initials: F
authors.lastname: Oerlemans
authors.forename: W
authors.initials: W
authors.lastname: van den Broek
authors.forename: B
authors.initials: B
authors.lastname: Gohlsch
authors.forename: D
authors.initials: D
authors.lastname: Pette
authors.forename: J J
authors.initials: JJ
authors.lastname: Plomp
authors.forename: P C
authors.initials: PC
authors.lastname: Molenaar
authors.forename: M G
authors.initials: MG
authors.lastname: Nederhoff
authors.forename: C J
authors.initials: CJ
authors.lastname: van Echteld
authors.forename: M
authors.initials: M
authors.lastname: Dekker
authors.forename: A
authors.initials: A
authors.lastname: Berns
authors.forename: H
authors.initials: H
authors.lastname: Hameister
authors.forename: B
authors.initials: B
authors.lastname: Wieringa
mesh_terms: D000818:Animals; D001483:Base Sequence; D006332:Cardiomegaly / Q000235:genetics / Q000473:pathology*; D018507:Gene Expression Regulation, Developmental; D006720:Homozygote; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D018485:Muscle Fibers, Skeletal / Q000473:pathology; D009154:Mutation; D009223:Myotonic Dystrophy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D014018:Tissue Distribution
chemical_list: C585517:DMPK protein, human; C585516:DMPK protein, mouse; D012333:RNA, Messenger; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases