Core B will breed and genotype CF mouse models including cftr and congenic derivatives thereof, CftrtmicAM>CftrG55iD] (^117^ gs we|| as FABP_numan CFTR+A transgenic (Tg) mice on a Cftr ^ background. The Core will also propagate a p11 knock-out mouse intended for studies of CFTR membrane recycling, and help P30 investigators test the influence of defective TGF-/? signaling on the CF phenotype using a TGF receptor-defective mouse characterized at our institution. New CF mice will be generated in the Core, including 'knock in'mouse models encoding prematurely truncated CFTR (Class I mutations). In addition, Tg(Scgb1a1-Scnn1b), a murine model exhibiting a CF-like pulmonary phenotype, will be provided to P30 investigators for projects such as those to investigate new mediators of inflammation in CF lung disease. Core B will also conduct testing with novel flexiVent equipment for assessing murine lung function. This system measures resistance, elastance, and compliance (and performs pressure-volume loop measurements of murine lungs), and can aerosolize compounds while simultaneously recording lung function in real-time. Like other laboratories, we have found that this sensitive equipment can discriminate CF from non-CF mice. The capabilities will allow us to evaluate new inflammatory pathways (HMGB1 and PGP) in CF airways. Preclinical assessment of CF therapies (PTC124) can be accomplished in the same way. Core B is experienced with bioelectric methods necessary to track changes in CFTR activity in vivo or ex vivo (transepithelial potential difference, short circuit current) and will provide these to P30 investigators who require the measurements for their CF research programs. In summary, Core B will provide mouse models and conduct state-of-the art assays necessary to examine CF disease mechanism in vivo, and facilitate preclinical evaluation of experimental therapeutics for the disease.
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| Duncan, Gregg A; Kim, Namho; Colon-Cortes, Yanerys et al. (2018) An Adeno-Associated Viral Vector Capable of Penetrating the Mucus Barrier to Inhaled Gene Therapy. Mol Ther Methods Clin Dev 9:296-304 |
| Gelfond, Daniel; Heltshe, Sonya L; Skalland, Michelle et al. (2018) Pancreatic Enzyme Replacement Therapy Use in Infants With Cystic Fibrosis Diagnosed by Newborn Screening. J Pediatr Gastroenterol Nutr 66:657-663 |
| Birket, Susan E; Davis, Joy M; Fernandez, Courtney M et al. (2018) Development of an airway mucus defect in the cystic fibrosis rat. JCI Insight 3: |
| Shei, Ren-Jay; Peabody, Jacelyn E; Kaza, Niroop et al. (2018) The epithelial sodium channel (ENaC) as a therapeutic target for cystic fibrosis. Curr Opin Pharmacol 43:152-165 |
| Gebert, Magdalena; Bartoszewska, Sylwia; Janaszak-Jasiecka, Anna et al. (2018) PIWI proteins contribute to apoptosis during the UPR in human airway epithelial cells. Sci Rep 8:16431 |
| Montoro, Daniel T; Haber, Adam L; Biton, Moshe et al. (2018) A revised airway epithelial hierarchy includes CFTR-expressing ionocytes. Nature 560:319-324 |
| Lutful Kabir, Farruk; Ambalavanan, Namasivayam; Liu, Gang et al. (2018) MicroRNA-145 Antagonism Reverses TGF-? Inhibition of F508del CFTR Correction in Airway Epithelia. Am J Respir Crit Care Med 197:632-643 |
| Shei, Ren-Jay; Peabody, Jacelyn E; Rowe, Steven M (2018) Functional Anatomic Imaging of the Airway Surface. Ann Am Thorac Soc 15:S177-S183 |
| Clancy, John Paul; Cotton, Calvin U; Donaldson, Scott H et al. (2018) CFTR modulator theratyping: Current status, gaps and future directions. J Cyst Fibros : |
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