Abstract

It is proposed to study, in depth, genetically determined myopathies, with particular emphasis on the following objectives; 1. Elucidation of the mechanism(s) responsible for determining whether genetically dystrophic (dy) murine muscle expresses or fails to express the dystrophic phenotype. 2. Determination of whether the inhibition of the degeneration- regeneration cycle which occurs when dystrophic (dy) muscle is transiently denervated is unique to this dystrophic mutant or whether a similar modification will occur in other diverse genetically determined myopathies (e.g., the mdx mouse and the dystrophic hamster). 3. Determination of the effect of inhibition of the degeneration- regeneration cycle of dystrophic (dy) myofibers on the development of proliferative senescence of myosatellite cells of these muscles. Determination whether the proliferative senescence of dy myosatellite cells in vitro is a result of the exhaustion of the mitotic capability of these cells during the early stage of the disease process or whether there is a primary defect in the myosatellite cells of dy muscles. 4. Evaluation of the extent of regeneration which occurs in the mdx mutant mouse. Evaluation of the mitotic capability of the myosatellite cells of the mdx muscle using clonal analysis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR036294-14
Application #
3157539
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1986-01-01
Project End
1991-12-31
Budget Start
1990-01-01
Budget End
1990-12-31
Support Year
14
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

Name
University of Pittsburgh
Department
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213

  Publications

DeRosimo, J F; Washabaugh, C H; Ontell, M P et al. (2000) Enhancement of adult muscle regeneration by primary myoblast transplantation. Cell Transplant 9:369-77
Chen, H H; Mack, L M; Choi, S Y et al. (1999) DNA from both high-capacity and first-generation adenoviral vectors remains intact in skeletal muscle. Hum Gene Ther 10:365-73
Floyd Jr, S S; Clemens, P R; Ontell, M R et al. (1998) Ex vivo gene transfer using adenovirus-mediated full-length dystrophin delivery to dystrophic muscles. Gene Ther 5:19-30
Yang, J; Kelly, R; Daood, M et al. (1998) Alteration in myosatellite cell commitment with muscle maturation. Dev Dyn 211:141-52
Chen, H H; Mack, L M; Kelly, R et al. (1997) Persistence in muscle of an adenoviral vector that lacks all viral genes. Proc Natl Acad Sci U S A 94:1645-50
Yang, J; Ontell, M P; Kelly, R et al. (1997) Limitations of nls beta-galactosidase as a marker for studying myogenic lineage or the efficacy of myoblast transfer. Anat Rec 248:40-50
Arcila, M E; Ameredes, B T; DeRosimo, J F et al. (1997) Mass and functional capacity of regenerating muscle is enhanced by myoblast transfer. J Neurobiol 33:185-98
Sopper, M M; Hauschka, S D; Hoffman, E et al. (1994) Gene complementation using myoblast transfer into fetal muscle. Gene Ther 1:108-13
Ontell, M P; Hughes, D; Hauschka, S D et al. (1992) Transient neonatal denervation alters the proliferative capacity of myosatellite cells in dystrophic (129ReJdy/dy) muscle. J Neurobiol 23:407-19
Ontell, M P; Moschella, M C; Schiaffino, S et al. (1992) Modification of the dystrophic phenotype after transient neonatal denervation: role of MHC isoforms. J Neurobiol 23:751-65

Showing the most recent 10 out of 17 publications