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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Methotrexate-resistant form of dihydrofolate reductase protects transgenic murine embryos from teratogenic effects of methotrexate.

Authors: Sutton, C; McIvor, R S; Vagt, M; Doggett, B; Kapur, R P

Published In Pediatr Dev Pathol, (1998 Nov-Dec)

Abstract: 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.

PubMed ID: 9724337 Exiting the NIEHS site

MeSH Terms: No MeSH terms associated with this publication

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