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JCI online early table of contents: March 6, 2008
Date:3/6/2008

; E-mail: steinma@mail.rockefeller.edu.

View the PDF of this article at: https://www.the-jci.org/article.php?id=34224


EDITOR'S PICK: Genetic manipulation might model cystic fibrosis

Cystic fibrosis (CF) is caused by mutations in the gene responsible for making the protein CFTR. Progress toward understanding the disease-causing mechanisms and developing new therapies has been hampered by the lack of a good animal model; e.g., CF mice fail to develop many of the symptoms seen in patients with CF. However, two independent reports in the April issue of the Journal of Clinical Investigation have described the first steps toward developing large animal (pig and ferret) models of the disease.

A team of researchers from the University of Iowa, Iowa City, and the University of Missouri Columbia, used recombinant adeno-associated virus (rAAV) vectors to alter the CFTR gene in pig fibroblasts such that was disrupted or contained the most common CF-associated mutation (delta-F508). The nucleus of these cells was used to fertilize the eggs of female pigs, and male piglets carrying one or other the mutated CFTR genes were generated. A similar approach rAAV targeting of the CFTR gene in ferret fibroblasts, followed by the transfer of the nucleus of the cells to the eggs of female ferrets was taken by John Engelhardt and colleagues, at the University of Iowa, Iowa City, to generate male ferrets carrying a mutated CFTR gene. As noted by the authors of both papers, these studies have not only provided animals that might lead to the development of a good animal model of CF, but also have described approaches that might be useful for the development of large animals models of other human genetic diseases.

TITLE: Production of CFTR-null and CFTR-delta-F508 heterozygous pigs by adeno-associated virusmediated gene ta
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