Rabbit model for cystic fibrosis

项目摘要 囊性纤维化(CF)动物模型对了解 潜在疾病的机制。然而，现有的CF动物模型有其局限性， 要么是因为动物模型不能复制人类的表型，要么是因为动物 车型的维护成本非常高，需要专门的护理。此外，缺乏良好的 ΔF508CFTR动物模型致病机制认识不清最常见 慢性萎缩性胃炎患者的突变，并阻止了慢性粒细胞白血病药物的发现。使用我们开发的CRISPR/CAS9 第一只兔的囊性纤维化跨膜电导调节器被破坏 (CFTR)。CFTR基因敲除兔的初步研究 (cftr-/-)显示了与人类cf患者相似的肺部病理。在此应用程序中， 目的：1、产生携带F508突变(F508/F508)的兔； 目的2，获得肠道校正CFtRF508/F508兔(TgCFtr-cftrF508/F508)； F508/F508兔的生物学特性拟议工作的成功将提供一个动物模型 为了了解潜在的分子机制，加速慢性粒细胞白血病药物的发现和 测试新药的疗效。 项目摘要/摘要第6页

Project Summary Cystic fibrosis (CF) animal models have contributed significantly to understanding the mechanism of underlying disease. However, existing CF animal models have their limitations, either because the animal models fail to reproduce human phenotypes or because the animal models have very high maintenance costs and need specialized care. In addition, lacking good ΔF508CFTR animal model results in poor understanding the pathogenesis of the most common mutation in CF patients and halts CF drug discovery. Using CRISPR/Cas9 we have developed the first rabbit with the disruption of cystic fibrosis transmembrane conductance regulator (CFTR). Initial work on CFTR knockout rabbits (CFTR-/-) revealed lung pathology that is similar to that in human CF patients. In this application, we will test: Aim 1, generate rabbits carrying F508 mutation (CFTRF508/F508) in CFTR locus; Aim 2, generate gut-corrected CFTRF508/F508 rabbits (TgCFTR-CFTRF508/F508); and Aim 3, characterize CFTRF508/F508 rabbits. The success of proposed work will provide an animal model for understanding the underlying molecular mechanisms, accelerating CF drug discovery and testing the efficacy of new drugs. Project Summary/Abstract Page 6