Differentially Expressed Genes Associated with 5-Aza-2′-Deoxycytidine-Induced Hindlimb Defects in the Swiss Webster Mouse

Stacy Branch, Bettina M. Francis, Mitchell B. Rosen, Cecil F. Brownie, Gary A. Held, Neil Chernoff

Research output: Contribution to journalArticlepeer-review


5-Aza-2′-deoxycytidine (d-AZA) inhibits methylation of DNA, a process that serves as an epigenetic regulator of gene expression. We have shown that d-AZA causes temporally related defects in mice. Gestational day (GD) 10 treatment induced severe long-bone defects of the hindlimb but not the forelimb. Exposure of younger embryos (GD 8 or 9) does not induce similar defects in forelimbs. This limb-dependent response suggests that methylation alterations in genes specific for fore- or hindlimbs may contribute to the observed pattern of defects. Subtraction hybridization (SH) studies were conducted to identify differential expression of DNA subsequent to the administration of d-AZA to mice on GD 10. Hindlimb buds collected from both treated and untreated embryos at 4, 12, and 24 hours post-treatment were used. A clone isolated from the untreated sample (down-regulation in treated tissue) was identified as a member of the murine B1 family of repetitive sequences. The two other clones isolated from the treated tissue (up-regulation) were homologous to avian myogenic regulatory protein mRNA and activin receptor type II gene. Both species are active during embryogenesis. These findings suggest that the isolated clones may have roles in abnormal embryonic development when inappropriately expressed.

Original languageEnglish (US)
Pages (from-to)135-141
Number of pages7
JournalJournal of Biochemical and Molecular Toxicology
Issue number3
StatePublished - 1998


  • 5-Aza-2′-deoxycytidine
  • Developmental Toxicology
  • Phocomelia
  • Subtractive Hybridization

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Toxicology
  • Health, Toxicology and Mutagenesis


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