GPC3--GENE STRUCTURE AND ROLE IN OVERGROWTH SYNDROMES

描述：(改编自调查人员的摘要) Simpson-Golabi-Behmel综合征(或SGBs)是一种巨人症/过度生长综合征 这使受影响的个人倾向于--想必是由于 组织肥大--与某些胚胎肿瘤的发展有关。这 这一建议是基于一种特定糖蛋白的损伤， Glypical3(GPC3)，引起该综合征。这是世界上第一个蛋白多糖 哪些损伤被证明会导致遗传病。 研究人员已经证明，GPC3在同一组织中高度表达 SGBS患者在没有胚胎组织的情况下倾向于过度生长，以及 已经获得证据表明它与胰岛素样生长因子2相互作用 (IGF2)。工作假设是在组织中，在时间和地点 当表达GPC3时，GPC3与IGF2的相互作用会影响 增长率。他们的目标是进一步分析GPC3基因的结构 和蛋白质，以及它们参与生长控制。拟议中的工作 结合对蛋白质及其相互作用的生物化学研究 IGF2，以及包括破坏GPC3基因和 为小鼠提供额外的转基因拷贝。这项工作还应该提供 SGB对表型的鉴别诊断试验 类似的Beckwith-Weidemann综合征，应该有助于分析 组织肥大和过度生长综合征的性质，并可提供 关于GPC3是否是某些肿瘤的抑制因子和可能的 为其他人做记号。

DESCRIPTION: (adapted from the investigator's abstract) Simpson-Golabi-Behmel Syndrome (or SGBS) is a gigantism/overgrowth syndrome that predisposes affected individuals -- presumably as a consequence of tissue hypertrophy -- to the development of certain embryonal tumors. This proposal is based on the finding that lesions in a particular glycoprotein, glypican 3 (GPC3), cause the syndrome. This is the first proteoglycan in which lesions are shown to result in genetic disease. The investigators have shown that GPC3 is highly expressed in the same embryonic tissues that tend to overgrow in its absence in SGBS patients, and have obtained evidence that it interacts with insulin-like growth factor 2 (IGF2). The working hypothesis is that in tissues where, and at the times when, GPC3 is expressed, an interaction of GPC3 with IGF2 influences the rate of growth. They aim to analyze further the structure of the GPC3 gene and protein, and their involvement in growth control. The proposed work uses a combination of biochemical studies of the protein and its interaction with IGF2, and genetic tests that include disruption of the GPC3 gene and provision of an extra transgenic copy in mice. The work should also provide diagnostic tests for the discrimination of SGBS for the phenotypically similar Beckwith-Weidemann Syndrome, should aid in the analysis of the nature of tissue hypertrophy and overgrowth syndromes, and can provide information about whether GPC3 is a suppressor of some tumors and a possible marker for others.