Loss of cftr function leads to pancreatic destruction in larval zebrafish.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Navis, A; Bagnat, M
Published Date
- March 15, 2015
Published In
Volume / Issue
- 399 / 2
Start / End Page
- 237 - 248
PubMed ID
- 25592226
Pubmed Central ID
- PMC4765326
Electronic International Standard Serial Number (EISSN)
- 1095-564X
Digital Object Identifier (DOI)
- 10.1016/j.ydbio.2014.12.034
Language
- eng
Conference Location
- United States