Cystic fibrosis in the mouse by targeted insertional mutagenesis

J R Dorin, P Dickinson, E W Alton, S N Smith, D M Geddes, B J Stevenson, W L Kimber, S Fleming, A R Clarke, M L Hooper

    Research output: Contribution to journalArticle

    223 Citations (Scopus)

    Abstract

    Cystic fibrosis is a fatal genetic disorder which afflicts 50,000 people worldwide. A viable animal model would be invaluable for investigating and combating this disease. The mouse cystic fibrosis transmembrane conductance regulator gene was disrupted in embryonal stem cells using an insertional gene targeting vector. Germ-line chimaeras were derived and the offspring of heterozygous crosses studied. These homozygous mutant mice survive beyond weaning. In vivo electrophysiology demonstrates the predicted defect in chloride ion transport in these mice and can distinguish between each genotype. Histological analysis detects important hallmarks of human disease pathology, including abnormalities of the colon, lung and vas deferens. This insertional mouse mutation provides a valid model system for the development and testing of therapies for cystic fibrosis patients.
    Original languageEnglish
    Pages (from-to)211-5
    Number of pages5
    JournalNature
    Volume359
    Issue number6392
    DOIs
    Publication statusPublished - 1992

    Fingerprint

    Insertional Mutagenesis
    Cystic Fibrosis
    Cystic Fibrosis Transmembrane Conductance Regulator
    Inborn Genetic Diseases
    Vas Deferens
    Gene Targeting
    Electrophysiology
    Ion Transport
    Regulator Genes
    Weaning
    Germ Cells
    Chlorides
    Colon
    Stem Cells
    Animal Models
    Genotype
    Pathology
    Lung
    Mutation
    Therapeutics

    Cite this

    Dorin, J. R., Dickinson, P., Alton, E. W., Smith, S. N., Geddes, D. M., Stevenson, B. J., ... Hooper, M. L. (1992). Cystic fibrosis in the mouse by targeted insertional mutagenesis. Nature, 359(6392), 211-5. https://doi.org/10.1038/359211a0
    Dorin, J R ; Dickinson, P ; Alton, E W ; Smith, S N ; Geddes, D M ; Stevenson, B J ; Kimber, W L ; Fleming, S ; Clarke, A R ; Hooper, M L. / Cystic fibrosis in the mouse by targeted insertional mutagenesis. In: Nature. 1992 ; Vol. 359, No. 6392. pp. 211-5.
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    abstract = "Cystic fibrosis is a fatal genetic disorder which afflicts 50,000 people worldwide. A viable animal model would be invaluable for investigating and combating this disease. The mouse cystic fibrosis transmembrane conductance regulator gene was disrupted in embryonal stem cells using an insertional gene targeting vector. Germ-line chimaeras were derived and the offspring of heterozygous crosses studied. These homozygous mutant mice survive beyond weaning. In vivo electrophysiology demonstrates the predicted defect in chloride ion transport in these mice and can distinguish between each genotype. Histological analysis detects important hallmarks of human disease pathology, including abnormalities of the colon, lung and vas deferens. This insertional mouse mutation provides a valid model system for the development and testing of therapies for cystic fibrosis patients.",
    author = "Dorin, {J R} and P Dickinson and Alton, {E W} and Smith, {S N} and Geddes, {D M} and Stevenson, {B J} and Kimber, {W L} and S Fleming and Clarke, {A R} and Hooper, {M L}",
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    Dorin, JR, Dickinson, P, Alton, EW, Smith, SN, Geddes, DM, Stevenson, BJ, Kimber, WL, Fleming, S, Clarke, AR & Hooper, ML 1992, 'Cystic fibrosis in the mouse by targeted insertional mutagenesis', Nature, vol. 359, no. 6392, pp. 211-5. https://doi.org/10.1038/359211a0

    Cystic fibrosis in the mouse by targeted insertional mutagenesis. / Dorin, J R; Dickinson, P; Alton, E W; Smith, S N; Geddes, D M; Stevenson, B J; Kimber, W L; Fleming, S; Clarke, A R; Hooper, M L.

    In: Nature, Vol. 359, No. 6392, 1992, p. 211-5.

    Research output: Contribution to journalArticle

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    AU - Stevenson, B J

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    AU - Fleming, S

    AU - Clarke, A R

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    Dorin JR, Dickinson P, Alton EW, Smith SN, Geddes DM, Stevenson BJ et al. Cystic fibrosis in the mouse by targeted insertional mutagenesis. Nature. 1992;359(6392):211-5. https://doi.org/10.1038/359211a0