Research Information

The first CF rat model, CFTR^tm1sage (termed CFTR-/- or KO), was designed in collaboration with SAGE (now Horizon Discovery) and subsequently characterized at UAB and distributed to the CF community. The model has been studied through 6 months of age and, based on its CF-like physiology, fills an important niche, enabling longitudinal evaluation in vivo, therapeutic testing, and mechanistic evaluations. We also have available humanized G551D CFTR (hG551D) rats that are sensitive to ivacaftor therapy and G542X CFTR rats that are subject to nonsense-mediated decay.

Sharma J, et al: A novel G542X CFTR rat model of cystic fibrosis is sensitive to nonsense mediated decay.
Birket SE, et al: Ivacaftor reverses airway mucus abnormalities in a rat model harboring a humanized G551D-CFTR.
Birket SE, et al.: Development of an airway mucus defect in the cystic fibrosis rat.
Tuggle KL et al.: Characterization of Defects in Ion Transport and Tissue Development in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)-Knockout Rats.

The CFTR Rat Models Core was established in 2018 in response to the need demonstrated by the CF community for support in the distribution and utilization of CF rats. Specifically, the Core is designed to fulfill two key functions:

Core Function #1: Breed, genotype, and distribute diverse CF rat models and tissues

• Breeding and distribution of CFTR^+/-, hG551D, and G542X rats, in addition to maintenance of wild-type Sprague Dawley strain for additional use

• Generation and procurement of novel relevant CF animal models to understand newly developed CFTR modulators, and to support continued studies of cell-based therapies, gene editing techniques, and additional approaches for rare CFTR mutations not yet addressed

Core Function #2: Conduct and develop endpoint measures to assess CFTR function, epithelial physiology, preclinical endpoints, and biospecimen analysis in CF rat models, with and without chronic lung infection

The Core provides the following state-of-the-art endpoints in CF rat models to elucidate disease mechanism, analyze pathways, or predict clinically relevant findings:

• CTFR physiological outcome measures (NPD, sweat secretion)

• Assays of lung structure and function (uCT imaging, Flexivent, in vivo microscopy)

• Collection and banking of biospecimen (survival bronchoscopy/BAL, blood, tissues, cryostat)

In addition, in conjunction with the RDP Gene Expression and RDP Functional Assay Cores, the Core develops systems to bridge studies from in vitro to in vivo use, including rat tracheal bronchial epithelial cell culture, nasal epithelial cell culture, and airway spheroid cultures. These systems increase throughput of initial studies and optimize conduct of in vivo experiments.

Contact Information

Core users are associated both within and beyond the CF Research Center; there is no limitation on who may access the Core. For additional information regarding resources and services, please contact:

Susan Birket, Pharm.D., Ph.D.

Director, CFTR Rat Models Core