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Loss of cftr function leads to pancreatic destruction in larval zebrafish.

Publication ,  Journal Article
Navis, A; Bagnat, M
Published in: Dev Biol
March 15, 2015

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.

Duke Scholars

Published In

Dev Biol

DOI

EISSN

1095-564X

Publication Date

March 15, 2015

Volume

399

Issue

2

Start / End Page

237 / 248

Location

United States

Related Subject Headings

  • Zebrafish
  • Pancreatic Ducts
  • Pancreas
  • Larva
  • In Situ Hybridization
  • Fluorescent Antibody Technique
  • Disease Models, Animal
  • Developmental Biology
  • DNA Primers
  • Cystic Fibrosis Transmembrane Conductance Regulator
 

Citation

APA
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ICMJE
MLA
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Navis, A., & Bagnat, M. (2015). Loss of cftr function leads to pancreatic destruction in larval zebrafish. Dev Biol, 399(2), 237–248. https://doi.org/10.1016/j.ydbio.2014.12.034
Navis, Adam, and Michel Bagnat. “Loss of cftr function leads to pancreatic destruction in larval zebrafish.Dev Biol 399, no. 2 (March 15, 2015): 237–48. https://doi.org/10.1016/j.ydbio.2014.12.034.
Navis A, Bagnat M. Loss of cftr function leads to pancreatic destruction in larval zebrafish. Dev Biol. 2015 Mar 15;399(2):237–48.
Navis, Adam, and Michel Bagnat. “Loss of cftr function leads to pancreatic destruction in larval zebrafish.Dev Biol, vol. 399, no. 2, Mar. 2015, pp. 237–48. Pubmed, doi:10.1016/j.ydbio.2014.12.034.
Navis A, Bagnat M. Loss of cftr function leads to pancreatic destruction in larval zebrafish. Dev Biol. 2015 Mar 15;399(2):237–248.
Journal cover image

Published In

Dev Biol

DOI

EISSN

1095-564X

Publication Date

March 15, 2015

Volume

399

Issue

2

Start / End Page

237 / 248

Location

United States

Related Subject Headings

  • Zebrafish
  • Pancreatic Ducts
  • Pancreas
  • Larva
  • In Situ Hybridization
  • Fluorescent Antibody Technique
  • Disease Models, Animal
  • Developmental Biology
  • DNA Primers
  • Cystic Fibrosis Transmembrane Conductance Regulator