STRUCTURE OF TYPE VI COLLAGEN AND ITS ROLE IN DISEASE

描述：（改编自研究者摘要）长期 本申请的目的是了解 研究VI型胶原是否参与了 结缔组织疾病 胶原VI是一种丰富的微纤维， 几乎存在于所有组织中。 它由三个 不同的链，[α 1（VI）α 2（VI）α 3（VI）]，由三个编码 位于人类染色体21和2上的基因。 在过去八 多年来，申请人已经阐明了蛋白质和基因结构， 人类胶原蛋白VI的三条链。 他们还发起了 关于胶原VI链的组装和调节的研究 VI型胶原基因表达。 越来越清楚的是， α 3（VI）基因在控制 胶原VI。 在这份续约申请中，他们建议继续 研究胶原蛋白的结构/功能，组装和调节 VI，主要强调α 3（VI）链。 他们还 建议使用转基因小鼠的方法来研究生物学 胶原VI在体内的作用和突变的表型后果 VI型胶原基因 本申请的具体目的是：1） 研究胶原VI的结构/功能和体外组装 使用在真核生物中产生的重组胶原蛋白链和结构域， 完成VI型胶原的表征 通过开发人类α 1（VI）的微卫星标记， α 2（VI）和α 3（VI）胶原基因并识别顺式和反式 调控元件控制转录和调节 人α 3（VI）基因; 3）研究人α 3（VI）基因的表达模式， 三个胶原VI链和选择性剪接变体中的三个胶原VI链， 小鼠;和4）研究胶原VI在体内的生物学作用， 胶原VI基因突变的表型后果， 制备和分析具有失活或突变的 α 3（VI）胶原基因。

DESCRIPTION: (Adapted from investigator's abstract) The long-term objectives of this application are to understand the biological function of collagen VI and to investigate whether collagen VI is involved in connective tissue disorders. Collagen VI is an abundant microfibrillar component present in almost all tissues. It is composed of three different chains, [alpha1(VI)alpha2(VI)alpha3(VI)], encoded by three genes located on human chromosome 21 and 2. During the past eight years, the applicants have elucidated the protein and gene structures for the three chains of human collagen VI. They also have initiated studies concerning the assembly of collagen VI chains and the regulation of collagen VI gene expression. It is becoming increasingly clear that the alpha3(VI) gene plays a key role in controlling the expression of collagen VI. In this renewal application, they propose to continue studying the structure/function, assembly, and regulation of collagen VI with a major emphasis placed on the alpha3(VI) chain. They also propose to use transgenic mice approaches to investigate the biological role of collagen VI in vivo and the phenotypic consequences of mutations in collagen VI genes. The Specific Aims of this application are: 1) to investigate the structure/function and assembly of collagen VI in vitro using recombinant collagen chains and domains produced in an eukaryotic expression system; 2) to complete the characterization of collagen VI genes by developing microsatellite markers for the human alpha1(VI), alpha2(VI) and alpha3(VI) collagen genes and identifying cis- and trans- regulatory elements controlling the transcription and regulation of the human alpha3(VI) gene; 3) to investigate the expression patterns of the three collagen VI chains and the alternative spliced variants in the mouse; and 4) to study the biological role of collagen VI in vivo and the phenotypic consequences of mutations in the collagen VI gene by preparing and analyzing transgenic mice with inactivated or mutated alpha3(VI) collagen gene.