Progress toward generating a ferret model of cystic fibrosis by somatic cell nuclear transfer
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BioMed Central
Open Access
Review
Progress toward generating a ferret model of cystic fibrosis by somatic cell nuclear transfer Ziyi Li1 and John F Engelhardt*1,2,3 Address: 1Department of Anatomy & Cell Biology, College of Medicine, University of Iowa, 1-111 BSB, 51 Newton Road, Iowa City, IA 52242, USA, 2Department of Internal Medicine, College of Medicine, University of Iowa, Iowa City, IA 52242, USA and 3The Center for Gene Therapy of Cystic Fibrosis and Other Genetic Diseases, College of Medicine, University of Iowa, Iowa City, IA 52242, USA Email: Ziyi Li - [email protected]; John F Engelhardt* - [email protected] * Corresponding author
Published: 07 November 2003 Reproductive Biology and Endocrinology 2003, 1:83
Received: 11 July 2003 Accepted: 07 November 2003
This article is available from: http://www.rbej.com/content/1/1/83 © 2003 Li and Engelhardt; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
Abstract Mammalian cloning by nuclear transfer from somatic cells has created new opportunities to generate animal models of genetic diseases in species other than mice. Although genetic mouse models play a critical role in basic and applied research for numerous diseases, often mouse models do not adequately reproduce the human disease phenotype. Cystic fibrosis (CF) is one such disease. Targeted ablation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in mice does not adequately replicate spontaneous bacterial infections observed in the human CF lung. Hence, several laboratories are pursuing alternative animal models of CF in larger species such as the pig, sheep, rabbits, and ferrets. Our laboratory has focused on developing the ferret as a CF animal model. Over the past few years, we have investigated several experimental parameters required for gene targeting and nuclear transfer (NT) cloning in the ferret using somatic cells. In this review, we will discuss our progress and the hurdles to NT cloning and gene-targeting that accompany efforts to generate animal models of genetic diseases in species such as the ferret.
Introduction Until recently, the generation of gene-targeted animal models has primarily relied upon homologous recombination following direct introduction of transgenes into embryonic stem cells (ES cells). While this technique has been successful for animal modeling in the mouse, it has thus far proven significantly more difficult in larger species. To date, the most exciting and promising research in transgenesis involves the use of fetal and adult somatic cells to produce genetically identical animals through nuclear transplantation [1,2]. Successful production of cloned animals derived from somatic cells was first demonstrated in sheep [3,4] and has more recently been demonstrated in mice [5], cattle [6], goats [7], pigs [8], cats [9], rabbits, [10] and mules [11]. Transgen
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