Abstract

This Program Project proposes a multidisciplinary approach to examine the function of several extracellular matrix (ECM) components of cartilage and bone by characterizing mice in which the genes for these components will have been disrupted by homologous recombination of embryonic stem cell. The program also proposes to use transgenic mice in order to study the mechanisms which control the tissue-specific expression of the genes for these components. Our goal is to capitalize on the strengths of the investigators, the complementary nature of the different projects and the powerful genetic approaches that are proposed to develop strongly interactive, collaborative projects. This program should help us gain considerable new knowledge about the mechanisms controlling the lineages and phenotypes of cells of skeletal tissues and about the function of individual cartilage and bone ECM components within larger multiprotein structures. These advances, which could not be effectively achieved by individual projects, should be very beneficial for our understanding of cartilage and bone diseases.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Program Projects (P01)
Project #
5P01AR042919-02
Application #
2390539
Study Section
Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
Project Start
1996-04-01
Project End
2000-03-31
Budget Start
1997-04-01
Budget End
1998-03-31
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
University of Texas MD Anderson Cancer Center
Department
Genetics
Type
Other Domestic Higher Education
DUNS #
001910777
City
Houston
State
TX
Country
United States
Zip Code
77030

  Publications

Coustry, Francoise; Oh, Chun-do; Hattori, Takako et al. (2010) The dimerization domain of SOX9 is required for transcription activation of a chondrocyte-specific chromatin DNA template. Nucleic Acids Res 38:6018-28
Nuka, S; Zhou, W; Henry, S P et al. (2010) Phenotypic characterization of epiphycan-deficient and epiphycan/biglycan double-deficient mice. Osteoarthritis Cartilage 18:88-96
Hattori, Takako; Coustry, Francoise; Stephens, Shelley et al. (2008) Transcriptional regulation of chondrogenesis by coactivator Tip60 via chromatin association with Sox9 and Sox5. Nucleic Acids Res 36:3011-24
Lee, Hu-Hui; Behringer, Richard R (2007) Conditional expression of Wnt4 during chondrogenesis leads to dwarfism in mice. PLoS One 2:e450
Govoni, Kristen E; Lee, Seong Keun; Chung, Yoon-Sok et al. (2007) Disruption of insulin-like growth factor-I expression in type IIalphaI collagen-expressing cells reduces bone length and width in mice. Physiol Genomics 30:354-62
Gebhard, Sonja; Hattori, Takako; Bauer, Eva et al. (2007) BAC constructs in transgenic reporter mouse lines control efficient and specific LacZ expression in hypertrophic chondrocytes under the complete Col10a1 promoter. Histochem Cell Biol 127:183-94
Kimura, Hiroaki; Akiyama, Haruhiko; Nakamura, Takashi et al. (2007) Tenascin-W inhibits proliferation and differentiation of preosteoblasts during endochondral bone formation. Biochem Biophys Res Commun 356:935-41
Akiyama, Haruhiko; Stadler, H Scott; Martin, James F et al. (2007) Misexpression of Sox9 in mouse limb bud mesenchyme induces polydactyly and rescues hypodactyly mice. Matrix Biol 26:224-33
Ovchinnikov, Dmitry A; Selever, Jennifer; Wang, Ying et al. (2006) BMP receptor type IA in limb bud mesenchyme regulates distal outgrowth and patterning. Dev Biol 295:103-15
Steiglitz, Barry M; Kreider, Jaclynn M; Frankenburg, Elizabeth P et al. (2006) Procollagen C proteinase enhancer 1 genes are important determinants of the mechanical properties and geometry of bone and the ultrastructure of connective tissues. Mol Cell Biol 26:238-49

Showing the most recent 10 out of 64 publications