INVESTIGATION OF THE ETIOLOGY OF MUCOLIPIDOSIS IV

粘脂贮积症 IV 的病因学调查

• 批准号: 2579613
• 负责人: E GOLDIN
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2579613
• 关键词: biomarker; cellular pathology; chloroquine; diagnosis design /evaluation; drug hypersensitivity; fibroblasts; gene complementation; gene mutation; genetic disorder diagnosis; genetic library; human tissue; inborn lipid storage disorder; inborn metabolism disorder diagnosis; molecular cloning; molecular pathology; mucopolysaccharidosis type IV; pathologic process; phenotype; prenatal diagnosis; tissue /cell culture; transfection

We have developed and validated a novel test for the prenatal diagnosis of mucolipidosis IV. The phenotypic alteration that permitted the development of this test is being used as a marker for the functional cloning of the gene that is mutated in mucolipidosis IV. In addition, we have designed a selection procedure for ML4 cells based on their increased sensitivity to chloroquine over normal control fibroblasts. This procedure will allow us to rapidly isolate complementing genes in ML4 cells transfected with DNA libraries. The increase in chloroquine sensitivity also provides a clue to the nature of the abnormal cell biology in patients with ML4.

我们开发并验证了一种新的产前诊断测试 粘脂沉积症 IV. 表型改变允许 该测试的开发被用作功能的标记 粘脂贮积症 IV 中突变的基因的克隆。 此外， 我们根据 ML4 细胞的情况设计了一个选择程序 与正常对照成纤维细胞相比，对氯喹的敏感性增加。 这个过程将使我们能够快速分离出互补基因 ML4 细胞转染 DNA 文库。氯喹的增加 敏感性还为异常细胞的性质提供了线索 ML4 患者的生物学。