GPC3--GENE STRUCTURE AND ROLE IN OVERGROWTH SYNDROMES

描述：（改编自研究者摘要） G-G-Behmel综合征（或SGBS）是一种发育不良/过度生长综合征， 这使受影响的个人倾向于--大概是由于 组织肥大--某些胚胎性肿瘤的发展。 这 该提议是基于这样的发现：在特定糖蛋白中的损伤， 磷脂酰肌醇蛋白聚糖3（GPC 3），引起综合征。 这是第一个蛋白聚糖， 这些病变被证明会导致遗传疾病。 研究人员已经表明，GPC 3在相同的细胞中高度表达。 在SGBS患者中，胚胎组织在缺乏时倾向于过度生长， 已经获得了它与胰岛素样生长因子2相互作用的证据 （IGF2）。 目前的假设是，在组织中， 当GPC 3表达时，GPC 3与IGF 2的相互作用会影响GPC 3的表达。 增长率。 他们的目标是进一步分析GPC 3基因的结构， 和蛋白质，以及它们在生长控制中的作用。 拟议工作 结合了对蛋白质及其相互作用的生物化学研究， 与IGF 2，和基因测试，包括破坏GPC 3基因， 在小鼠中提供额外的转基因拷贝。 这项工作还应提供 用于区分SGBS表型的诊断测试 类似的Beckwith-Weidemann综合征，应有助于分析 组织肥大和过度生长综合征的性质，并可以提供 关于GPC 3是否是某些肿瘤的抑制因子以及可能的 为他人做标记。

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.