Journal article
Adeno-associated virus–targeted disruption of the CFTR gene in cloned ferrets
The Journal of clinical investigation, Vol.118(4), pp.1578-1583
04/01/2008
DOI: 10.1172/JCI34599
PMCID: PMC2263147
PMID: 18324338
Abstract
Somatic cell gene targeting combined with nuclear transfer cloning presents tremendous potential for the creation of new, large-animal models of human diseases. Mouse disease models often fail to reproduce human phenotypes, underscoring the need for the generation and study of alternative disease models. Mice deficient for CFTR have been poor models for cystic fibrosis (CF), lacking many aspects of human CF lung disease. In this study, we describe the production of a
CFTR
gene–deficient model in the domestic ferret using recombinant adeno-associated virus–mediated gene targeting in fibroblasts, followed by nuclear transfer cloning. As part of this approach, we developed a somatic cell rejuvenation protocol using serial nuclear transfer to produce live CFTR-deficient clones from senescent gene-targeted fibroblasts. We transferred 472 reconstructed embryos into 11 recipient jills and obtained 8 healthy male ferret clones heterozygous for a disruption in exon 10 of the
CFTR
gene. To our knowledge, this study represents the first description of genetically engineered ferrets and describes an approach that may be of substantial utility in modeling not only CF, but also other genetic diseases.
Details
- Title: Subtitle
- Adeno-associated virus–targeted disruption of the CFTR gene in cloned ferrets
- Creators
- Xingshen Sun - Department of Anatomy and Cell Biology andZiying Yan - Department of Anatomy and Cell Biology andYaling Yi - Department of Anatomy and Cell Biology andZiyi Li - Department of Anatomy and Cell Biology andDiana Lei - Department of Anatomy and Cell Biology andChristopher S Rogers - Department of Anatomy and Cell Biology andJuan Chen - Department of Anatomy and Cell Biology andYulong Zhang - Department of Anatomy and Cell Biology andMichael J Welsh - Department of Anatomy and Cell Biology andGregory H Leno - Department of Anatomy and Cell Biology andJohn F Engelhardt - Department of Anatomy and Cell Biology and
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.118(4), pp.1578-1583
- Publisher
- American Society for Clinical Investigation
- DOI
- 10.1172/JCI34599
- PMID
- 18324338
- PMCID
- PMC2263147
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Language
- English
- Date published
- 04/01/2008
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Anatomy and Cell Biology; Radiation Oncology; Neurosurgery; Internal Medicine
- Record Identifier
- 9984020643002771
Metrics
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