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Updated: Jul 6, 2026
Adenovirus-mediated Genetic Removal of Signaling Molecules in Cultured Primary Mouse Embryonic Fibroblasts
Published on: September 9, 2010
Adeno-associated virus-targeted disruption of the CFTR gene in cloned ferrets
Xingshen Sun1, Ziying Yan, Yaling Yi
1Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.
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.
Insights
Scientists created the first genetically engineered ferrets lacking the CFTR gene, offering a new large-animal model for cystic fibrosis (CF) and other genetic diseases.
Area of Science:
- Genetics
- Animal Models
- Biotechnology
Background:
- Mouse models often fail to accurately replicate human diseases.
- Existing CFTR gene-deficient mice poorly model human cystic fibrosis lung disease.
- Large-animal models are needed for better human disease research.
Purpose of the Study:
- To develop a CFTR gene-deficient ferret model.
- To establish a method for creating genetically engineered ferrets.
- To provide a novel large-animal model for cystic fibrosis and other genetic disorders.
Main Methods:
- Somatic cell gene targeting using recombinant adeno-associated virus in ferret fibroblasts.
- Nuclear transfer cloning to create genetically modified ferrets.
- Somatic cell rejuvenation protocol using serial nuclear transfer for senescent cells.
Main Results:
- Successfully produced CFTR gene-deficient ferret clones.
- Generated 8 healthy male ferret clones heterozygous for a CFTR exon 10 disruption.
- Developed a viable method for creating genetically engineered ferrets.
Conclusions:
- Genetically engineered ferrets can be produced using gene targeting and nuclear transfer.
- This study establishes the first genetically engineered ferret model.
- The approach offers significant potential for modeling cystic fibrosis and other genetic diseases in a relevant large-animal system.
