Mouse models have become increasingly valuable for biomedical research, and their importance is particularly relevant to cystic fibrosis science as attested to by scores of publications describing studies performed on these models as a means to understand and treat the human disease. The Animal Models Core Facility provides a variety of mouse lines to CF P30 investigators, including previously generated and characterized strains that include the UNC (Cftr[tm1Unc]) and Cambridge (Cftr[tm1Cam]) Cftr knockout;Cftr-G551D (Cftr[Tm1G551D]);Cftr-F508del line (Cftr[Tm1Kth]);a transgenic (Tg) line expressing wild type human CFTR on a Cftr[-/-] background (hCFTR Cftr[-/-]), and a similar Tg mouse line expressing a human CFTR-G542X on a Cftr[-/-] background (hCFTR-G542X Cftr[-/-]). In addition to these established mouse lines available at our Center, we have assisted P30 investigators with the generation and/or breeding of several novel CF mouse models, including a Cftr-G542X knock-in line (Cftr[Tm1G542X]) and a Tg line expressing human CFTR-W1282X in a Cftr[-/-] background (hCFTR-W1282X Cftr[-/-]). A number of other murine lines are presently under construction in Core B. The Animal Models Core also assists CF investigators by providing functional CFTR assays, including nasal Potential Difference (PD) measurements assays in live animals as well as intestinal short circuit current assays of freshly excised tissues. The overall purpose of the Animal Models Core is to provide all necessary murine resources for the successful completion of individual P30 projects, and to perform advanced physiologic and other testing of CF animal models. These resources allow investigators to examine CF disease mechanism in vivo, and facilitate preclinical evaluation of experimental therapeutics for the disease. Thus, the Animal Models Core is an indispensable component of the overall P30.

Public Health Relevance

Core B provides animal models, electrophysiologic equipment, solutions, and resources to be shared among many investigators without the need to duplicate the same capabilities in multiple laboratories. The Core has been indispensable for research priorities delineated by the overall UAB P30, including studies of CFTR cellular biology, tissue pathogenesis, and clinical translation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Center Core Grants (P30)
Project #
2P30DK072482-06
Application #
8320678
Study Section
Special Emphasis Panel (ZDK1-GRB-7 (J1))
Project Start
Project End
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
6
Fiscal Year
2012
Total Cost
$325,230
Indirect Cost
$103,230
Name
University of Alabama Birmingham
Department
Type
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Wang, Wei; Hong, Jeong S; Rab, Andras et al. (2016) Robust Stimulation of W1282X-CFTR Channel Activity by a Combination of Allosteric Modulators. PLoS One 11:e0152232
Mutyam, Venkateshwar; Libby, Emily Falk; Peng, Ning et al. (2016) Therapeutic benefit observed with the CFTR potentiator, ivacaftor, in a CF patient homozygous for the W1282X CFTR nonsense mutation. J Cyst Fibros :
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Veit, Gudio; Avramescu, Radu G; Chiang, Annette N et al. (2016) From CFTR biology toward combinatorial pharmacotherapy: expanded classification of cystic fibrosis mutations. Mol Biol Cell 27:424-33
Solomon, George M; Raju, S Vamsee; Dransfield, Mark T et al. (2016) Therapeutic Approaches to Acquired Cystic Fibrosis Transmembrane Conductance Regulator Dysfunction in Chronic Bronchitis. Ann Am Thorac Soc 13 Suppl 2:S169-76
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