Abstract

The long term goal of this project is to understand how skeletal muscle differentiation is regulated.
The specific aims are to determine how certain growth factors repress muscle differentiation, how proliferating myoblasts become """"""""committed"""""""" to a post-mitotic state when specific mitogens are withdrawn, and how the M- and B-creatine kinase genes are regulated during terminal muscle differentiation. Major methodologies used in this project are: cell culture, growth factor receptor analysis, mutant selection, somatic genetics, gene cloning, gene sequencing, gene structural analysis, fusion and mutant gene construction, introduction of genes into cells, and analysis of endogenous and exogenous gene expression. Health-related aspects of the project are its contribution toward the understanding of normal development and gene expression. Possible medical applications are to developmental disorders, to genetic diseases, to degenerative muscle diseases, to normal and neoplastic growth regulation and to general clinical diagnostic procedures involving M- and B-creatine kinase.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR018860-11
Application #
3154999
Study Section
Molecular Cytology Study Section (CTY)
Project Start
1976-05-01
Project End
1987-11-30
Budget Start
1986-12-01
Budget End
1987-11-30
Support Year
11
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
University of Washington
Department
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195

  Publications

Amoasii, Leonela; Long, Chengzu; Li, Hui et al. (2017) Single-cut genome editing restores dystrophin expression in a new mouse model of muscular dystrophy. Sci Transl Med 9:
Muir, Lindsey A; Nguyen, Quynh G; Hauschka, Stephen D et al. (2014) Engraftment potential of dermal fibroblasts following in vivo myogenic conversion in immunocompetent dystrophic skeletal muscle. Mol Ther Methods Clin Dev 1:14025
Hu, Chuhong; Kasten, Jennifer; Park, Hana et al. (2014) Myocyte-mediated arginase expression controls hyperargininemia but not hyperammonemia in arginase-deficient mice. Mol Ther 22:1792-802
Gantz, Jay A; Palpant, Nathan J; Welikson, Robert E et al. (2012) Targeted genomic integration of a selectable floxed dual fluorescence reporter in human embryonic stem cells. PLoS One 7:e46971
Himeda, Charis L; Tai, Phillip W L; Hauschka, Stephen D (2012) Analysis of muscle gene transcription in cultured skeletal muscle cells. Methods Mol Biol 798:425-43
Tai, Phillip W L; Smith, Catherine L; Angello, John C et al. (2012) Analysis of fiber-type differences in reporter gene expression of ?-gal transgenic muscle. Methods Mol Biol 798:445-59
Tai, Phillip Wl; Fisher-Aylor, Katherine I; Himeda, Charis L et al. (2011) Differentiation and fiber type-specific activity of a muscle creatine kinase intronic enhancer. Skelet Muscle 1:25
Gonçalves, Manuel A F V; Janssen, Josephine M; Nguyen, Quynh G et al. (2011) Transcription factor rational design improves directed differentiation of human mesenchymal stem cells into skeletal myocytes. Mol Ther 19:1331-41
Himeda, Charis L; Chen, Xiaolan; Hauschka, Stephen D (2011) Design and testing of regulatory cassettes for optimal activity in skeletal and cardiac muscles. Methods Mol Biol 709:3-19
Himeda, Charis L; Ranish, Jeffrey A; Pearson, Richard C M et al. (2010) KLF3 regulates muscle-specific gene expression and synergizes with serum response factor on KLF binding sites. Mol Cell Biol 30:3430-43

Showing the most recent 10 out of 45 publications