Intermediate filaments are cell-type specific, and desmin is the intermediate filament found in muscle. This investigator, who has studied desmin since she discovered and characterized the desmin gene as a postdoctoral fellow with Lazarides, has prepared a mouse knockout for desmin. Defects in muscle architecture are observed, and the mice are viable, permitting further analysis, which is now proposed. The application includes three Aims; all designed to test the major current hypotheses for the function of desmin intermediate filaments in muscle.
The aims i nclude morphologic and physiologic studies of the knockout mice.
Aim 1 is to study how the muscle defects in the desmin knockout mice arise, by examining mice through prenatal development. Skeletal, cardiac and smooth muscle will be examined. Morphology of the myofibrillar apparatus and expression of muscle-specific genes will be examined.
Aim 2 is to examine the morphology of the abnormal muscle, using electron microscopy. Both muscle from animals and cultured cell systems will be utilized. The questions are how the fine structure of the myofibril and its interaction with membranes and mitochondria are disturbed by the lack of desmin.
Aim 3 is to study the functional properties of the muscle in the desmin knockout mouse, examining standard physiological parameters associated with skeletal, smooth and cardiac muscle. In addition, the ability of the muscle to repair following injury will be examined.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR039617-12
Application #
6171236
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Program Officer
Lymn, Richard W
Project Start
1988-07-15
Project End
2002-08-31
Budget Start
2000-09-01
Budget End
2001-08-31
Support Year
12
Fiscal Year
2000
Total Cost
$268,031
Indirect Cost
Name
Baylor College of Medicine
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
Diokmetzidou, Antigoni; Soumaka, Elisavet; Kloukina, Ismini et al. (2016) Desmin and ?B-crystallin interplay in the maintenance of mitochondrial homeostasis and cardiomyocyte survival. J Cell Sci 129:3705-3720
Capetanaki, Yassemi; Papathanasiou, Stamatis; Diokmetzidou, Antigoni et al. (2015) Desmin related disease: a matter of cell survival failure. Curr Opin Cell Biol 32:113-20
Tsoupri, Elsa; Capetanaki, Yassemi (2013) ?yospryn: a multifunctional desmin-associated protein. Histochem Cell Biol 140:55-63
Capetanaki, Yassemi; Bloch, Robert J; Kouloumenta, Asimina et al. (2007) Muscle intermediate filaments and their links to membranes and membranous organelles. Exp Cell Res 313:2063-76
Ralston, E; Lu, Z; Biscocho, N et al. (2006) Blood vessels and desmin control the positioning of nuclei in skeletal muscle fibers. J Cell Physiol 209:874-82
Fountoulakis, Michael; Soumaka, Elisavet; Rapti, Kleopatra et al. (2005) Alterations in the heart mitochondrial proteome in a desmin null heart failure model. J Mol Cell Cardiol 38:461-74
Weisleder, Noah; Taffet, George E; Capetanaki, Yassemi (2004) Bcl-2 overexpression corrects mitochondrial defects and ameliorates inherited desmin null cardiomyopathy. Proc Natl Acad Sci U S A 101:769-74
Weisleder, Noah; Soumaka, Elisavet; Abbasi, Shahrzad et al. (2004) Cardiomyocyte-specific desmin rescue of desmin null cardiomyopathy excludes vascular involvement. J Mol Cell Cardiol 36:121-8
Capetanaki, Yassemi (2002) Desmin cytoskeleton: a potential regulator of muscle mitochondrial behavior and function. Trends Cardiovasc Med 12:339-48
Mavroidis, Manolis; Capetanaki, Yassemi (2002) Extensive induction of important mediators of fibrosis and dystrophic calcification in desmin-deficient cardiomyopathy. Am J Pathol 160:943-52

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