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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. <\/jats:p>","DOI":"10.1007\/s100249900069","type":"journal-article","created":{"date-parts":[[2002,7,25]],"date-time":"2002-07-25T06:40:57Z","timestamp":1027579257000},"page":"503-512","source":"Crossref","is-referenced-by-count":14,"title":["Methotrexate-Resistant Form of Dihydrofolate Reductase Protects Transgenic Murine Embryos from Teratogenic Effects of Methotrexate"],"prefix":"10.1177","volume":"1","author":[{"given":"Cari","family":"Sutton","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Washington, Seattle, WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. 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