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Mislocalization of ΔF508 CFTR in cystic fibrosis sweat gland

Nature Genetics volume 1, pages 321–327 (1992)Cite this article

Abstract

Misprocessing and mislocalization of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) has been described for the major CF–causing mutation (ΔF508) in heterologous expression systems in vitro. We have generated monoclonal antibodies (mAbs) to CFTR with the aim of localizing the protein and its CF variants in vivo. Of the tissues where CFTR was observed, only the sweat gland is readily available and does not undergo secondary changes due to CF disease pathology. Sweat ducts from CF patients homozygous for ΔF508 did not show the typical apical membrane staining seen in control biopsies. This demonstrates that the biosynthetic arrest and intracellular retention of ΔF508 GFTR initially observed in vitro does occur in vivo and emphasizes the need to focus efforts on understanding the mislocalization.

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Authors and Affiliations

  1. Research Institute, The Hospital for Sick Children, Toronto, Ontario, M5G 1X8, Canada

    Norbert Kartner & John R. Riordan

  2. Cystic Fibrosis Research Development Program, The Hospital for Sick Children, Toronto, Ontario, M5G 1X8, Canada

    Norbert Kartner, Olga Augustinas & John R. Riordan

  3. Department of Biochemistry, The Hospital for Sick Children, Toronto, Ontario, M5G 1X8, Canada

    Norbert Kartner, Timothy J. Jensen & A. Leonard Naismith

  4. Departments of Biochemistry and Clinical Biochemistry, University of Toronto, Toronto, Ontario, M5S 1A8, Canada

    John R. Riordan

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  1. Norbert Kartner
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  2. Olga Augustinas
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  4. A. Leonard Naismith
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  5. John R. Riordan
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Kartner, N., Augustinas, O., Jensen, T. et al. Mislocalization of ΔF508 CFTR in cystic fibrosis sweat gland. Nat Genet 1, 321–327 (1992). https://doi.org/10.1038/ng0892-321

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