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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Vermeer, Daniel W. Sigmund, Curt D. Ostedgaard, Lynda S. Welsh, Michael J. Meyerholz, David K. Schneider, Lindsey Karp, Philip H. |
| Description | Author Affiliation: Ostedgaard LS ( Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.); |
| Abstract | Gene transfer could provide a novel therapeutic approach for cystic fibrosis (CF), and adeno-associated virus (AAV) is a promising vector. However, the packaging capacity of AAV limits inclusion of the full-length cystic fibrosis transmembrane conductance regulator (CFTR) cDNA together with other regulatory and structural elements. To overcome AAV size constraints, we recently developed a shortened CFTR missing the N-terminal portion of the R domain (residues 708-759, CFTRΔR) and found that it retained regulated anion channel activity in vitro. To test the hypothesis that CFTRΔR could correct in vivo defects, we generated CFTR(-/-) mice bearing a transgene with a fatty acid binding protein promoter driving expression of human CFTRΔR in the intestine (CFTR(-/-);TgΔR). We found that intestinal crypts of CFTR(-/-);TgΔR mice expressed CFTRΔR and the intestine appeared histologically similar to that of WT mice. Moreover, like full-length CFTR transgene, the CFTRΔR transgene produced CFTR Cl(-) currents and rescued the CFTR(-/-) intestinal phenotype. These results indicate that the N-terminal part of the CFTR R domain is dispensable for in vivo intestinal physiology. Thus, CFTRΔR may have utility for AAV-mediated gene transfer in CF. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 7 |
| Volume Number | 108 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2011-02-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cystic Fibrosis Transmembrane Conductance Regulator Genetics Cystic Fibrosis Therapy Genetic Therapy Protein Structure, Tertiary Animals Dependovirus Electrophoresis, Polyacrylamide Gel Electrophysiology Genetic Vectors Immunohistochemistry Intestines Anatomy & Histology Metabolism Mice Mice, Knockout Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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