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Citation
Kim, K., Lane, E.A., Saftien, A., Wang, H., Xu, Y., Wirtz-Peitz, F., Perrimon, N. (2020). Drosophila as a model for studying cystic fibrosis pathophysiology of the gastrointestinal system.  Proc. Natl. Acad. Sci. U.S.A. 117(19): 10357--10367.
FlyBase ID
FBrf0245682
Publication Type
Research paper
Abstract

Cystic fibrosis (CF) is a recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. The most common symptoms include progressive lung disease and chronic digestive conditions. CF is the first human genetic disease to benefit from having five different species of animal models. Despite the phenotypic differences among the animal models and human CF, these models have provided invaluable insight into understanding disease mechanisms at the organ-system level. Here, we identify a member of the ABCC4 family, CG5789, that has the structural and functional properties expected for encoding the Drosophila equivalent of human CFTR, and thus refer to it as Drosophila CFTR (Dmel\CFTR). We show that knockdown of Dmel\CFTR in the adult intestine disrupts osmotic homeostasis and displays CF-like phenotypes that lead to intestinal stem cell hyperplasia. We also show that expression of wild-type human CFTR, but not mutant variants of CFTR that prevent plasma membrane expression, rescues the mutant phenotypes of Dmel\CFTR Furthermore, we performed RNA sequencing (RNA-Seq)-based transcriptomic analysis using Dmel\CFTR fly intestine and identified a mucin gene, Muc68D, which is required for proper intestinal barrier protection. Altogether, our findings suggest that Drosophila can be a powerful model organism for studying CF pathophysiology.

PubMed ID
PubMed Central ID
PMC7229672 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Proc. Natl. Acad. Sci. U.S.A.
    Title
    Proceedings of the National Academy of Sciences of the United States of America
    Publication Year
    1915-
    ISBN/ISSN
    0027-8424
    Data From Reference
    Alleles (23)
    Genes (8)
    Human Disease Models (1)
    Natural transposons (1)
    Insertions (11)
    Experimental Tools (4)
    Transgenic Constructs (23)