Methotrexate-resistant form of dihydrofolate reductase protects transgenic murine embryos from teratogenic effects of methotrexate
| Autor: | Micki Vagt, Cari Sutton, Barbara Doggett, R. Scott McIvor, Raj P. Kapur |
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| Rok vydání: | 1998 |
| Předmět: |
Male
Tail Limb Buds Transgene Cell Count Mice Transgenic Aminopterin Pathology and Forensic Medicine Amethopterin 03 medical and health sciences Mice 0302 clinical medicine Pregnancy Culture Techniques Dihydrofolate reductase Forelimb medicine Animals Enzyme Inhibitors chemistry.chemical_classification 030219 obstetrics & reproductive medicine biology Abnormalities Drug-Induced Gene Expression Regulation Developmental Embryo General Medicine Embryonic stem cell Molecular biology Hindlimb Tetrahydrofolate Dehydrogenase Enzyme Methotrexate Teratogens chemistry Drug Resistance Neoplasm 030220 oncology & carcinogenesis Pediatrics Perinatology and Child Health biology.protein Female medicine.drug |
| Zdroj: | Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society. 1(6) |
| ISSN: | 1093-5266 |
| Popis: | Methotrexate, a potent inhibitor of the ubiquitously expressed enzyme dihydrofolate reductase, induces limb and facial anomalies that resemble vascular disruptions in their evolution and final outcome. Previous studies suggest that inhibition of dihydrofolate reductase is responsible for methotrexate-induced embryopathy, although specific sites of methotrexate activity have not been well defined. In this report, we show that constitutive expression of a methotrexate-resistant form of dihydrofolate reductase in transgenic embryos and their placentas ameliorates methotrexate teratogenicity. However, expression of the transgene in maternal tissues had no significant protective effect. The results confirm the role of dihydrofolate reductase inhibition in the pathogenesis of methotrexate-induced birth defects and provide a foundation for future studies of targeted transgene expression in select embryonic or placental cell populations. |
| Databáze: | OpenAIRE |
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