STRUCTURE OF TYPE VI COLLAGEN AND ITS ROLE IN DISEASE

描述：(改编自调查人员摘要)长期 本应用程序的目的是了解生物功能 以及研究VI型胶原是否参与了 结缔组织疾病。VI型胶原是一种丰富的微纤维 几乎存在于所有组织中的成分。它由三个部分组成 不同的链，[Alpha1(VI)Alpha2(VI)Alpha3(VI)]，由三个 位于人类21号和2号染色体上的基因。在过去的八年里 多年来，申请者已经阐明了蛋白质和基因结构 人类六型胶原蛋白的三条链。他们还启动了 VI型胶原链的组装及其调控研究 VI型胶原基因的表达。越来越清楚的是， α3(VI)基因在调控HSP70基因表达中起关键作用 在这次续签申请中，他们建议继续 研究胶原蛋白的结构/功能、组装和调节 VI，重点放在字母3(VI)链上。他们还 建议使用转基因小鼠的方法来研究生物学 VI型胶原在体内的作用及其突变的表型后果 在VI型胶原基因中。本申请的具体目的是：1) VI型胶原的结构/功能及其体外组装研究 使用在真核生物中产生的重组胶原链和结构域 表达系统；2)完成VI型胶原蛋白的鉴定 通过开发人类α1(VI)的微卫星标记， α2(VI)和Alpha3(VI)胶原基因及其顺式和反式胶原的鉴定 控制转录和调控的调控元件 3)研究人α3(VI)基因的表达模式 三条VI型胶原链及其选择性剪接变异体 4)研究VI型胶原在体内的生物学作用； VI型胶原基因突变的表型后果 失活或突变的转基因小鼠的制备和分析 α3(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.