Targeted inactivation of plectin reveals essential function in maintaining the integrity of skin, muscle, and heart cytoarchitecture
- Kerstin Andrä1,
- Hans Lassmann2,
- Reginald Bittner3,
- Sigrid Shorny3,
- Reinhard Fässler4,
- Friedrich Propst1, and
- Gerhard Wiche1,5
- 1Institute of Biochemistry and Molecular Cell Biology, Vienna Biocenter, 1030 Vienna, Austria; 2Institute of Neurology, University of Vienna, 1090 Vienna, Austria; 3Institute for Anatomy, Neuromuscular Department, University of Vienna, 1090 Vienna, Austria; 4Department of Proteinchemistry, Max-Planck-Institute for Biochemistry, 82152 Martinsried, Germany
Abstract
Previous studies suggest that plectin, a versatile cytoskeletal linker protein, has an important role in maintaining the structural integrity of diverse cells and tissues. To establish plectin’s function in a living organism, we have disrupted its gene in mice. Plectin (−/−) mice died 2–3 days after birth exhibiting skin blistering caused by degeneration of keratinocytes. Ultrastructurally, hemidesmosomes and desmosomes appeared unaffected. In plectin-deficient mice, however, hemidesmosomes were found to be significantly reduced in number and apparently their mechanical stability was altered. The skin phenotype of these mice was similar to that of patients suffering from epidermolysis bullosa simplex (EBS)-MD, a hereditary skin blistering disease with muscular dystrophy, caused by defects in the plectin gene. In addition, plectin (−/−) mice revealed abnormalities reminiscent of minicore myopathies in skeletal muscle and disintegration of intercalated discs in heart. Our results clearly demonstrate a general role of plectin in the reinforcement of mechanically stressed cells. Plectin (−/−) mice will provide a useful tool for the study of EBS-MD, and possibly other types of plectin-related myopathies involving skeletal and cardiac muscle, in an organism amenable to genetic manipulation.
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Footnotes
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↵5 Corresponding author.
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E-MAIL wiche{at}abc.univie.ac.at; FAX 43-1-79515-5121.
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- Received June 12, 1997.
- Accepted September 25, 1997.
- Cold Spring Harbor Laboratory Press
