THE ROLE OR TYPE XXVII COLLAGEN IN SKELETOGENESIS

XXVII 型胶原蛋白在骨骼生成中的作用

• 批准号: 7173023
• 负责人: JAMES M PACE
• 金额: $ 7.19万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7173023
• 关键词: Ablation; Biological; Biological Process; Biology; Blood Vessels; Bone Development; Bone Growth; Bone and Cartilage Funding; C-terminal; Cardiovascular system; Cartilage; Cells; Cessation of life; Characteristics; Chondrogenesis; Chondrosarcoma; Class; Collagen; Collagen Gene; Collagen Type I; Collagen Type II; Collagen Type XI; Congenital Abnormality; Connective Tissue; Connective Tissue Diseases; Data; Defect; Development; Disease; Drug or chemical Tissue Distribution; Ear; Ehlers-Danlos Syndrome; Electron Microscopy; Epidermolysis Bullosa; Evolution; Exons; Extracellular Matrix; Eye; Family; Fibrillar Collagen; Future; Gene Mutation; Genes; Gold; Grant; Hereditary nephritis; Homo; Human; Immunohistochemistry; In Situ Hybridization; Introns; Invertebrates; Investigation; Lead; Length; Link; Location; Maintenance; Metaphyseal chondrodysplasia; Molecular Profiling; Multiple Epiphyseal Dysplasias; Mus; Mutate; Mutation; Myopathy; Names; Nature; Neonatal; Optics; Organ; Osteogenesis Imperfecta; Paper; Pathogenesis; Pattern; Phylogenetic Analysis; Post-Translational Protein Processing; Pregnancy; Procollagen; Production; Protein Family; Proteins; Rattus; Reading; Reverse Transcriptase Polymerase Chain Reaction; Role; Rupture; Skeletal system; Skin; Structure; Syndrome; Testing; Tissues; base; bone; capsule; crosslink; day; disease phenotype; editorial; genome sequencing; insight; link protein; long bone; member; novel; scaffold; size

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）： COL 27 A1是一个新发现的基因，编码XXVII型胶原蛋白的前α链。它是胶原纤维形成类的成员，其中每个成员都与骨骼、皮肤或心血管系统的疾病有关。COL 27 A1在进化过程中是保守的，在人类胶原蛋白中，最接近无脊椎动物纤维胶原蛋白基因，暗示了重要的生物学功能。初步数据表明，COL 27 A1主要在软骨中表达，包括骨的原基，以及在眼睛和视神经囊中。这种表达模式让人想起II型和XI型胶原基因，当突变时会导致软骨发育不良。因此，我们假设XXVII型胶原蛋白，像其他纤维状胶原蛋白一样，是这些组织的细胞外基质（ECM）的重要组成部分，从而使COL 27 A1成为软骨形成和骨、眼和耳发育异常的疾病的极好候选位点。为了开始检验这一假设，将完成三个具体目标。首先，XXVII型胶原蛋白将从培养的大鼠软骨肉瘤细胞中分离出来，并根据其翻译后修饰和三聚体分子的性质进行生物化学表征。其次，将通过RT-PCR、原位杂交和免疫组织化学确定COL 27 A1的发育特异性组织表达谱。第三，XXVII型胶原相对于细胞外基质其他成员的位置将通过免疫金电子显微镜和交联蛋白质的质谱分析来确定。这些研究是必要的，以推动该领域的发展，并将提供新的见解软骨，骨骼，光学和耳组织的发展。他们还将为未来研究XXVII型胶原蛋白的确切生物学作用及其与脊椎骨骺和干骺端软骨发育不良等结缔组织疾病发病机制的联系铺平道路。