Rabbit model for cystic fibrosis

兔囊性纤维化模型

• 批准号: 10420741
• 负责人: Jian-Ping Jin
• 金额: $ 16.59万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-05 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10420741
• 关键词: Rabbit; model; cystic; fibrosis

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

项目摘要 囊性纤维化（CF）动物模型已经显著地促进了对囊性纤维化的理解。 潜在疾病的机制。然而，现有的CF动物模型有其局限性， 或者是因为动物模型不能复制人类表型，或者是因为动物 模型的维护成本非常高，需要专门的护理。此外，缺乏良好的 Δ F508 CFTR动物模型的发病机制最常见的结果是认识不足 突变的CF患者和停止CF药物的发现。使用CRISPR/Cas9，我们开发了 第一只囊性纤维化跨膜传导调节因子被破坏的兔子 （CFTR）。CFTR敲除兔的初步工作 （CFTR-/-）显示肺病理学与人CF患者相似。在本申请中， 我们将进行以下试验：目的1，制备携带CFTR基因突变（CFTR突变F508/CFTR突变F508）的家兔; 目的2，产生肠道校正的CFTR CFR 508/CFR 508兔（TgCFTR-CFTR CFR 508/CFR 508）;和目的3， 表征CFTR CF 1F 508/CF 1F 508兔。这项工作的成功将提供一种动物模型， 了解潜在的分子机制，加速CF药物的发现， 测试新药的功效 项目摘要/摘要第6页

项目成果

Bacterial and Pneumocystis Infections in the Lungs of Gene-Knockout Rabbits with Severe Combined Immunodeficiency.

• DOI: 10.3389/fimmu.2018.00429
• 发表时间: 2018
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Song J;Wang G;Hoenerhoff MJ;Ruan J;Yang D;Zhang J;Yang J;Lester PA;Sigler R;Bradley M;Eckley S;Cornelius K;Chen K;Kolls JK;Peng L;Ma L;Chen YE;Sun F;Xu J
• 通讯作者: Xu J

Intestinal Dysbiosis in Young Cystic Fibrosis Rabbits.

• DOI: 10.3390/jpm11020132
• 发表时间: 2021-02-16
• 期刊: Journal of personalized medicine
• 作者: Liang X;Bouhamdan M;Hou X;Zhang K;Song J;Hao K;Jin JP;Zhang Z;Xu J
• 通讯作者: Xu J

Production of CFTR-ΔF508 Rabbits.

CFTR-ΔF508兔子的产生。

• DOI: 10.3389/fgene.2020.627666
• 发表时间: 2020
• 期刊: Frontiers in genetics
• 影响因子: 3.7
• 作者: Yang D;Liang X;Pallas B;Hoenerhoff M;Ren Z;Han R;Zhang J;Chen YE;Jin JP;Sun F;Xu J
• 通讯作者: Xu J

Production of immunodeficient rabbits by multiplex embryo transfer and multiplex gene targeting.

• DOI: 10.1038/s41598-017-12201-0
• 发表时间: 2017-09-22
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Song J;Yang D;Ruan J;Zhang J;Chen YE;Xu J
• 通讯作者: Xu J

Dissection of the Role of VIMP in Endoplasmic Reticulum-Associated Degradation of CFTRΔF508.

VIMP 在内质网相关 CFTRÎF508 降解中作用的剖析

• DOI: 10.1038/s41598-018-23284-8
• 发表时间: 2018-03-19
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Hou X;Wei H;Rajagopalan C;Jiang H;Wu Q;Zaman K;Xie Y;Sun F
• 通讯作者: Sun F