A high G418-resistantneoRtransgenic mouse and mouse embryonic fibroblast (MEF) feeder layers for cytotoxicity and gene targetingin vivoandin vitro
| العنوان: | A high G418-resistantneoRtransgenic mouse and mouse embryonic fibroblast (MEF) feeder layers for cytotoxicity and gene targetingin vivoandin vitro |
|---|---|
| المؤلفون: | Kevin A. Johnson, Jiri Aubrecht, Elizabeth M. Simpson, Mary E. P. Goad, Charles P. Lerner, Agnieszka K. Czopik, Robert H. Schiestl |
| المصدر: | Drug and Chemical Toxicology. 34:433-439 |
| بيانات النشر: | Informa UK Limited, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Genetically modified mouse, Cell Survival, Health, Toxicology and Mutagenesis, Transgene, Drug Resistance, Mice, Transgenic, Biology, Toxicology, Median lethal dose, Lethal Dose 50, Mice, In vivo, Toxicity Tests, Acute, medicine, Animals, Transgenes, Promoter Regions, Genetic, Cells, Cultured, Pharmacology, Chemical Health and Safety, Kanamycin Kinase, Lethal dose, Public Health, Environmental and Occupational Health, Feeder Cells, Gene targeting, General Medicine, Neomycin, Fibroblasts, biochemical phenomena, metabolism, and nutrition, Molecular biology, In vitro, Mice, Inbred C57BL, Blotting, Southern, Gene Targeting, embryonic structures, Gentamicins, Plasmids, medicine.drug |
| الوصف: | Aminoglycoside antibiotics have been in use since 1944 with the discovery of streptomycin. The aim of this study was to derive a new, highly resistant multicopy neo(R) transgenic mouse strain, named TgN3Ems, by random insertion of the plasmid, pPGKneobpA, and compare the level of drug resistance of wild-type and transgenic mice in vivo and corresponding primary mouse embryonic fibroblasts (MEFs) in vitro to a model neomycin analog, G418. The expression neoR in transgenic animals caused a 5-fold increase in the approximate lethal dose of G418, compared to wild type. No adverse pathological changes were found for the transgenic mice treated with G418, as they all died within minutes after injection. In contrast, the G418 treatment of wild-type mice resulted in a marked liver and kidney toxicity detected microscopically and via increases of serum biomarkers for liver and kidney damage. In addition, there was a mild bone marrow and lymphoid depletion. In in vitro studies, the transgenic MEFs survived 20-fold higher G418 levels, compared to the wild-type MEF cells. Therefore, TgN3Ems transgenic mice could be used as a source of G418-resistant feeder cells for gene targeting. Since the expression of drug-resistance genes in transgenic animals confers resistance to toxicity, the TgN3Ems mice might serve as a tool applicable in drug design. |
| تدمد: | 1525-6014 0148-0545 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7f6ccaeb3e3c1451985cc5defc3e10fc https://doi.org/10.3109/01480545.2010.544316 |
| رقم الأكسشن: | edsair.doi.dedup.....7f6ccaeb3e3c1451985cc5defc3e10fc |
| قاعدة البيانات: | OpenAIRE |
PDF full text from Publisher | تدمد: | 15256014 01480545 |
|---|