(from the application): The long term goal of this program is to understand the molecular mechanisms controlling skeletogenesis and to characterize genes involved in embryonic skeletal patterning with the belief that such knowledge may ultimately aid in the prevention, detection and treatment of skeletal disorders. In Drosophila, certain of the major mesodermal lineages are specified by the bagpipe homeobox gene, which is a DNA-binding transcriptional regulator. We have recently isolated from mouse and human, homologues of the bagpipe gene designated Bapxl and BAPX1, respectively. We have mapped murine Bapxl to the proximal end of mouse chromosome 5 and human BAPX1 to 4p16, a region containing loci for several skeletal disorders. Bapxl encodes a predicted protein of 333 amino acids and expression of Bapxl RNA is first detectable in E8.0 embryos in the mesoderm of the most newly formed somites in the group of cells corresponding to the presclerotome, the precursor of the vertebrae. Thus Bapxl is one of the earliest developmental markers for the sclerotome portion of the somite. Bapxl continues to be expressed well into organogenesis in essentially all cartilaginous condensations which will subsequently undergo endochondral bone formation of the axial, appendicular and facial skeleton. The expression pattern of Bapxl in murine embryos suggests that there are evolutionary conserved mechanisms of mesoderm specification and differentiation and that the mammalian Bapxl gene has likely acquired an important developmental role in chondrogenesis and skeletal patterning. To investigate the developmental role of the Bapxl gene, we will undertake the following specific aims: (I) To complete the characterization of the genomic organization, chromosomal localization, and embryonic expression pattern of the Bapxl homeobox gene in both mouse and human. (II) To investigate the developmental role of the Bapxl gene in chondrogenesis and embryonic skeletal patterning, by generating a loss-of-function null mutation (gene knockout) of the Bapxl gene in mice.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Small Research Grants (R03)
Project #
5R03AR045035-03
Application #
6055674
Study Section
Special Emphasis Panel (ZAR1-TNL-A (O1))
Program Officer
Sharrock, William J
Project Start
1997-09-15
Project End
2000-08-31
Budget Start
1999-09-01
Budget End
2000-08-31
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Biochemistry
Type
Schools of Medicine
DUNS #
114400633
City
New York
State
NY
Country
United States
Zip Code
10029