Development of a porcine model of cystic fibrosis

Michael J Welsh; Christopher S Rogers; David A Stoltz; David K Meyerholz; Randall S Prather

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Journal article

Development of a porcine model of cystic fibrosis

Michael J Welsh, Christopher S Rogers, David A Stoltz, David K Meyerholz and Randall S Prather

Transactions of the American Clinical and Climatological Association, Vol.120, pp.149-162

2009

PMCID: PMC2744522

PMID: 19768173

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Abstract

Cystic Fibrosis (CF) is a common autosomal recessive disease that affects multiple organs. The lack of an animal model with manifestations like those typically found in humans has slowed understanding of its pathogenesis. Therefore, because of the similarities between human and swine anatomy, biochemistry, physiology, size, and genetics, we chose to develop a porcine model of CF. We used homologous recombination in primary cultures of porcine fibroblasts to disrupt the CFTR gene and then used those cells as nuclear donors for somatic cell nuclear transfer. After crossing heterozygous pigs, we produced CFTR-/- pigs. The newborn CFTR null piglets manifested meconium ileus, pancreatic destruction, early focal biliary cirrhosis, and gall bladder abnormalities that were very similar to those observed in humans with CF. At birth, there were no abnormalities in the airway epithelium or submucosal glands and no evidence of inflammation, consistent with findings in the newborn human. We hope that this porcine model will help elucidate the pathogenesis of CF and thereby lead to the development of new mechanism-based therapies.

Respiratory System - pathology

Gene Targeting - methods

Gallbladder Diseases - pathology

Ileus - genetics

Species Specificity

Humans

Cystic Fibrosis - pathology

Liver Diseases - pathology

Gallbladder Diseases - genetics

Cystic Fibrosis - etiology

Pancreatic Diseases - pathology

Gallbladder Diseases - etiology

Swine

Ileus - etiology

Liver Diseases - etiology

Cystic Fibrosis Transmembrane Conductance Regulator - deficiency

Pancreatic Diseases - etiology

Infant, Newborn

Disease Models, Animal

Animals, Newborn

Liver Diseases - genetics

Animals, Genetically Modified

Cystic Fibrosis - metabolism

Pancreatic Diseases - genetics

Phenotype

Animals

Models, Biological

Respiratory System - metabolism

Cystic Fibrosis - genetics

Meconium

Cystic Fibrosis Transmembrane Conductance Regulator - genetics

Mutation

Details

Title: Subtitle: Development of a porcine model of cystic fibrosis
Creators: Michael J Welsh - Howard Hughes Medical Institute 500 EMRB, Roy J. and Lucille A. Carver College of Medicine University of Iowa Iowa City, IA 52242, USA. michael-welsh@uiowa.edu
Christopher S Rogers
David A Stoltz
David K Meyerholz
Randall S Prather
Resource Type: Journal article
Publication Details: Transactions of the American Clinical and Climatological Association, Vol.120, pp.149-162
Publisher: United States
PMID: 19768173
PMCID: PMC2744522
ISSN: 0065-7778
Language: English
Date published: 2009
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Pathology; Neurosurgery; Internal Medicine
Record Identifier: 9984025404202771

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