Muscle atrophy in Titin M-line deficient mice

J. Peng, K. Raddatz, S. Labeit, Hendrikus "Henk" Granzier, M. Gotthardt

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

We investigated the response to deletion of the titin M-line region in striated muscle, using a titin knockout model and a range of techniques that include histology, in situ hybridization, electron microscopy, and 2D gel analysis. We found that the loss of titin's kinase domain and binding sites for myomesin and MURF-1 causes structural changes in the sarcomere that proceed from the M-line to the Z-disc and ultimately result in disassembly of the sarcomere. Disassembly goes along with central localization of nuclei (a hallmark for muscular dystrophy), up-regulation of heat-shock proteins, and induction of proteasome activity. While fiber type composition does not change in soleus and extensor digitorum longus muscle, fiber size is reduced. Animals die from complications of muscle atrophy at five weeks of age. In addition to the structural importance of the titin M-line region in any striated muscle, our data show how differences in M-line composition between heart and skeletal muscle affect sarcomere stability and function.

Original languageEnglish (US)
Pages (from-to)381-388
Number of pages8
JournalJournal of Muscle Research and Cell Motility
Volume26
Issue number6-8
DOIs
StatePublished - Dec 2005
Externally publishedYes

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Connectin
Muscular Atrophy
Muscle
Sarcomeres
Striated Muscle
Histology
Muscular Dystrophies
Fibers
Proteasome Endopeptidase Complex
Heat-Shock Proteins
Chemical analysis
Electron microscopy
In Situ Hybridization
Myocardium
Electron Microscopy
Animals
Skeletal Muscle
Up-Regulation
Gels
Binding Sites

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

Muscle atrophy in Titin M-line deficient mice. / Peng, J.; Raddatz, K.; Labeit, S.; Granzier, Hendrikus "Henk"; Gotthardt, M.

In: Journal of Muscle Research and Cell Motility, Vol. 26, No. 6-8, 12.2005, p. 381-388.

Research output: Contribution to journalArticle

Peng, J. ; Raddatz, K. ; Labeit, S. ; Granzier, Hendrikus "Henk" ; Gotthardt, M. / Muscle atrophy in Titin M-line deficient mice. In: Journal of Muscle Research and Cell Motility. 2005 ; Vol. 26, No. 6-8. pp. 381-388.
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