RRC ID 33628
著者 Navis A, Bagnat M.
タイトル Loss of cftr function leads to pancreatic destruction in larval zebrafish.
ジャーナル Dev Biol
Abstract The development and function of many internal organs requires precisely regulated fluid secretion. A key regulator of vertebrate fluid secretion is an anion channel, the cystic fibrosis transmembrane conductance regulator (CFTR). Loss of CFTR function leads to defects in fluid transport and cystic fibrosis (CF), a complex disease characterized by a loss of fluid secretion and mucus buildup in many organs including the lungs, liver, and pancreas. Several animal models including mouse, ferret and pig have been generated to investigate the pathophysiology of CF. However, these models have limited accessibility to early processes in the development of CF and are not amenable for forward genetic or chemical screens. Here, we show that Cftr is expressed and localized to the apical membrane of the zebrafish pancreatic duct and that loss of cftr function leads to destruction of the exocrine pancreas and a cystic fibrosis phenotype that mirrors human disease. Our analyses reveal that the cftr mutant pancreas initially develops normally, then rapidly loses pancreatic tissue during larval life, reflecting pancreatic disease in CF. Altogether, we demonstrate that the cftr mutant zebrafish is a powerful new model for pancreatitis and pancreatic destruction in CF. This accessible model will allow more detailed investigation into the mechanisms that drive CF of the pancreas and facilitate development of new therapies to treat the disease.
巻・号 399(2)
ページ 237-48
公開日 2015-3-15
DOI 10.1016/j.ydbio.2014.12.034
PII S0012-1606(15)00004-4
PMID 25592226
PMC PMC4765326
MeSH Acinar Cells / pathology Animals Animals, Genetically Modified Body Weights and Measures Chromosomes, Artificial, Bacterial Cystic Fibrosis / genetics* Cystic Fibrosis / physiopathology Cystic Fibrosis Transmembrane Conductance Regulator / genetics Cystic Fibrosis Transmembrane Conductance Regulator / metabolism* DNA Primers / genetics Disease Models, Animal* Fluorescent Antibody Technique In Situ Hybridization Larva / growth & development Pancreas / growth & development Pancreas / pathology* Pancreatic Ducts / cytology Zebrafish / genetics* Zebrafish / growth & development*
IF 2.896
引用数 27
WOS 分野 DEVELOPMENTAL BIOLOGY
リソース情報
ゼブラフィッシュ Tg(UAS:GFP)?