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

Cari Sutton, R S Mc Ivor, Micki Vagt, Barbara Doggett, Raj P. Kapur

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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 thepathogenesis of methotrexate-induced birth defects and provide a foundation for future studies of targeted transgene expression in select embryonic or placental cell populations.

Original languageEnglish (US)
Pages (from-to)503-512
Number of pages10
JournalPediatric and Developmental Pathology
Volume1
Issue number6
DOIs
StatePublished - Jan 1 1998

Keywords

  • Amethopterin
  • Aminopterin
  • Ectrodactyly
  • Frontonasal dysplasia
  • Malformation
  • Teratogen
  • Vascular disruption

Fingerprint Dive into the research topics of 'Methotrexate-resistant form of dihydrofolate reductase protects transgenic murine embryos from teratogenic effects of methotrexate'. Together they form a unique fingerprint.

Cite this