論文 - 詳細
| RRC ID | 59041 |
|---|---|
| 著者 | Kim K, Lane EA, Saftien A, Wang H, Xu Y, Wirtz-Peitz F, Perrimon N. |
| タイトル | Drosophila as a model for studying cystic fibrosis pathophysiology of the gastrointestinal system. |
| ジャーナル | Proc Natl Acad Sci U S A |
| 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. |
| 巻・号 | 117(19) |
| ページ | 10357-10367 |
| 公開日 | 2020-5-12 |
| DOI | 10.1073/pnas.1913127117 |
| PII | 1913127117 |
| PMID | 32345720 |
| PMC | PMC7229672 |
| MeSH | Animals Cystic Fibrosis / genetics Cystic Fibrosis / metabolism Cystic Fibrosis / pathology* Cystic Fibrosis Transmembrane Conductance Regulator / genetics Cystic Fibrosis Transmembrane Conductance Regulator / metabolism* Disease Models, Animal* Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster High-Throughput Nucleotide Sequencing Homeostasis Humans Intestines / pathology* Mucins / genetics Mucins / metabolism Mutation* Phenotype Stem Cells / metabolism Stem Cells / pathology* |
| IF | 9.412 |
| 引用数 | 0 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 16 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ショウジョウバエ | 5789R-1 5789R-4 |