MOLECULAR ANALYSIS OF LANGER-GIEDION SYNDROME

Langer-Giedio 综合征的分子分析

• 批准号: 2403235
• 负责人: DAN E WELLS
• 金额: $ 19.22万
• 依托单位: UNIVERSITY OF HOUSTON
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-01 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2403235
• 关键词: Mus musculus; achondroplasia; bone development; carcinogenesis; chromosome deletion; congenital skeletal disorder; cytogenetics; developmental genetics; family genetics; gene expression; gene rearrangement; gene targeting; genetic polymorphism; genetically modified animals; human genetic material tag; human tissue; in situ hybridization; linkage mapping; molecular pathology; northern blottings; nucleic acid sequence; phenotype; polymerase chain reaction; pulsed field gel electrophoresis; southern blotting

DESCRIPTION (Adapted from the Investigator's Abstract): Langer-Giedion syndrome is characterized by cone-shaped epiphyses in the hand, multiple cartilaginous exostoses, shortness of stature, and characteristic craniofacial abnormalities, and mental retardation. The clinical features of Langer-Giedion syndrome are essentially identical to those of trichorhinophalangeal syndrome type I except that the latter does not include multiple exostoses and rarely includes mental retardation. The exostoses found in LGS are essentially identical to those seen in hereditary multiple exostoses, an autosomal dominant disorder characterized by multiple, cartilage-capped exostoses (benign tumors) on the juxtaepiphyseal regions of enchondral bones. The long term goal of this research project is the complete characterization at the molecular level of the genes which are responsible for the phenotypes associated with the Langer-Giedion syndrome and the related syndromes hereditary multiple exostoses and trichorhinophalangeal syndrome type 1. This application encompasses the following three specific aims which are directed at our long term goal. First is to isolate and characterize the genes located in the LGS region including TRPSI and any genes that may be involved in normal mental function. Second, isolate and characterize the gene for EXT2 present on chromosome 11 and look for clues as to how its function is related to EXT1. Third, use the mouse as a model system to analyze the role of EXT1 in bone development and tumorigenesis. Characterize the temporal and spatial pattern of EXT1 expression in the mouse using both RNA blot and in situ hybridization techniques determine the role this gene plays in vivo by analyzing mice with a null mutation in the EXT1 gene. The genes involved in the pathology of Langer-Giedion syndrome are likely to be involved in the normal development of bone and connective tissues and of normal mental capabilities. Understanding the functions of these genes may give us insights into these important developmental processes as well as tumor suppression. Molecular analysis of the Langer-Giedion genes will be an essential step towards a detailed understanding of their functions.

描述（改编自研究者摘要）：Langer-Giedion 综合征的特点是锥形骨骺在手中，多个 软骨性外生骨疣，身材矮小， 颅面畸形和智力迟钝 的临床特点 Langer-Giedion综合征的发病率与 毛鼻指综合征I型，除了后者不 包括多发性外生骨疣，很少包括智力迟钝。 的 在LGS中发现的外生骨疣基本上与在遗传性 多发性外生骨疣，一种常染色体显性遗传疾病， 多发性，软骨帽外生骨疣（良性肿瘤）在近骺 软骨内骨骼的区域。 本研究项目的长期目标是 基因在分子水平上的完整表征， 与Langer-Giedion综合征相关的表型 以及遗传性多发性外生骨疣的相关综合征， 发鼻指综合征1型。 此应用程序包括 这三个目标都是针对我们的长远目标。 首先是分离和鉴定位于LGS区域的基因 包括TRPSI和任何可能与正常精神 功能 第二，分离并表征存在于大肠杆菌中的EXT 2基因。 11号染色体，并寻找其功能如何与EXT 1相关的线索。 第三，以小鼠为模型系统，分析EXT 1在骨中的作用 发育和肿瘤发生。 描述时间和空间 使用RNA印迹和原位杂交的小鼠中EXT 1表达模式 杂交技术确定了该基因在体内的作用， 分析EXT 1基因无效突变的小鼠。 相关基因 Langer-Giedion综合征的病理学可能涉及 骨骼和结缔组织以及正常智力的正常发育 能力的 了解这些基因的功能可能会给我们 深入了解这些重要的发育过程以及肿瘤 镇压 对Langer-Giedion基因的分子分析将是一项重要的研究。 这是深入了解其功能的重要一步。