EPITHELIAL CELL LINES WITH CYSTIC FIBROSIS MUTATIONS

囊性纤维化是一种常见的致命遗传性疾病， 囊性纤维化跨膜调节因子（CFTR）的不同突变 基因，并且与进行性肺病经典相关， 胰腺外分泌功能不全汗液氯离子水平升高 一些 突变与不寻常的临床表型相关，包括轻度 肺部疾病、胰腺功能不全和/或汗液Cl-正常。 的 正常CFTR和突变CFTR与 可以在体外系统中有效地评估轻度或严重的疾病， 保持差异化的特性与那些本地的 组织中 拟议项目的总体目标是发展 上皮细胞系，来自 具有特定CFTR突变的患者，并确定和部分 表征保留分化表型特性的细胞系 反映了体内状态。 纯合子罕见CFTR受试者 与轻度疾病相关的突变已经同意， 参与这项研究。 呼吸道和汗腺上皮细胞 将培养小的活检标本并用逆转录病毒感染 携带乳头状瘤，延长培养细胞的寿命，但有小 对表型特性的影响。 生长能力增强的细胞 将被选择，传播，并筛选保留一个 分化良好的表型。 离子传输能力和其他 将评估最佳品系的特征，并且细胞将 提供给合作研究者进行其他研究 旨在阐明某些CFTR突变 导致轻微疾病。

Cystic fibrosis is a common lethal genetic disease that is caused by different mutations in the Cystic Fibrosis Transmembrane Regulator (CFTR) gene and is classically associated with progressive lung disease, exocrine pancreatic insufficiency, and elevated sweat Cl- levels. Some mutations are associated with unusual clinical phenotypes, including mild lung disease, pancreatic sufficiency, and/or normal sweat Cl-. The mechanisms by which normal CFTR and CFTR with mutations associated with mild or severe disease may evaluated effectively in in vitro systems that maintain differentiated properties comparable to those of the native tissues. The overall objective of the proposed project is to develop epithelial cell lines from airway epithelia and sweat gland epithelia of patients with specific CFTR mutations, and to identify and partially characterize cell lines that retain differentiated phenotypic properties reflective of the in vivo state. Subjects with homozygous rare CFTR mutations that are associated with mild disease have agreed to participate in this study. Airway and sweat gland epithelial cells from small biopsy specimens will be cultured and infected with a retrovirus carrying papilloma which extend the life of cultured cells but have small effects on phenotypic properties. Cells with increased growth capability will be selected, propagated, and screened for retention of a well-differentiated phenotype. Ion transport capabilities and other characteristics of the best lines will be evaluated, and the cells will be supplied to collaborating investigators for additional studies designed to elucidate the mechanisms by which certain CFTR mutations confer mild disease.