COL27A1 is a newly discovered gene that encodes a pro-alpha chain of type XXVII collagen. It is a member of the fibril-forming class of collagens, of which each member is linked to a disease of the skeletal, integumentary, or cardiovascular systems. COL27A1 is conserved through evolution and among human collagens, most closely resembles invertebrate fibrillar collagen genes, suggestive of an important biological function. Preliminary data indicate that COL27A1 is expressed primarily in cartilage, including the anlagen of bone, and in the eye and optic capsule. This pattern of expression is reminiscent of the type II and XI collagen genes, which when mutated result in forms of chondrodysplasia. Thus, we hypothesize that type XXVII collagen, like the other fibrillar collagens, is an essential component of the extracellular matrices (ECM) of these tissues, thereby making COL27A1 an excellent candidate locus for disorders in which abnormalities in chondrogenesis, and bone, ocular and otic development occur. To begin testing this hypothesis three specific aims will be accomplished. First, type XXVII collagen will be isolated from cultured rat chondrosarcoma cells and biochemically characterized in terms of its post-translational modifications and the nature of its trimeric molecule. Second, a developmentally specific tissue expression profile of COL27A1 will be determined by RT-PCR, in situ hybridization, and immunohistochemistry. Third, the location of type XXVII collagen in relation to other members of the extracellular matrix will be determined by immuno-gold electron microscopy, and by mass spectrometric analysis of cross-linked proteins. These studies are necessary to advance the field and will provide novel insights into the development of cartilaginous, skeletal, optic, and otic tissues. They will also pave the way for future investigations into the exact biological role of type XXVII collagen and its link to the pathogenesis of connective tissue diseases such as the spondyloepiphyseal and metaphyseal chondrodysplasias.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Small Research Grants (R03)
Project #
5R03AR052476-03
Application #
7173023
Study Section
Special Emphasis Panel (ZAR1-GHZ-D (J2))
Program Officer
Tyree, Bernadette
Project Start
2005-04-01
Project End
2008-07-31
Budget Start
2007-02-01
Budget End
2008-07-31
Support Year
3
Fiscal Year
2007
Total Cost
$71,872
Indirect Cost
Name
University of Washington
Department
Pathology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Christiansen, Helena E; Lang, Michael R; Pace, James M et al. (2009) Critical early roles for col27a1a and col27a1b in zebrafish notochord morphogenesis, vertebral mineralization and post-embryonic axial growth. PLoS One 4:e8481
Hjorten, Rebecca; Hansen, Uwe; Underwood, Robert A et al. (2007) Type XXVII collagen at the transition of cartilage to bone during skeletogenesis. Bone 41:535-42