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Generation and characterization of a ΔF508 cystic fibrosis mouse model

Nature Genetics volume 10, pages 445–452 (1995)Cite this article

Abstract

We have generated mice carrying the most common mutation in cystic fibrosis (CF), ΔF508, within the cystic fibrosis (Cftr) gene. Mutant animals show pathological and electrophysiological changes consistent with a CF phenotype. ΔF508−/− mice die from peritonitis and show deficiencies in cAMP–activated electrogenic Cl− transport. These mice produce ΔF508 transcripts and show the temperature–dependent trafficking defect first described for the human ΔF508 CFTR protein. A functional CFTR Cl− channel not demonstrated by null CF mice or present at 37 °C was detected following incubation of epithelial cells at 27 °C. Thus, these mice are an accurate ΔF508 model and will be valuable for testing drugs aimed at overcoming the ΔF508 trafficking defect.

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Author notes

  1. William H. Colledge

    Present address: Department of Physiology, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK

Authors and Affiliations

  1. Wellcome/CRC Institute of Cancer and Developmental Biology and Department of Genetics, University of Cambridge, Tennis Court Rd., Cambridge, CB2 1QR, UK

    William H. Colledge, Benjamin S. Abella, Rosemary Ratcliff & Martin J. Evans

  2. Department of Pharmacology, University of Cambridge, Tennis Court Rd., Cambridge, CB2 1QJ, UK

    Kevin W. Southern, Lesley J. MacVinish & Alan W. Cuthbert

  3. Genzyme Corporation, One Mountain Road, Framingham, Massachusetts, 017101-9322, USA

    Canwen Jiang & Seng H. Cheng

  4. Department of Histopathology, Addenbrookes Hospital, Hills Rd., Cambridge, CB2 2QQ, UK

    Janice R. Anderson

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Colledge, W., Abella, B., Southern, K. et al. Generation and characterization of a ΔF508 cystic fibrosis mouse model. Nat Genet 10, 445–452 (1995). https://doi.org/10.1038/ng0895-445

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  • DOI: https://doi.org/10.1038/ng0895-445

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