A mouse model for valproate teratogenicity: Parental effects, homeotic transformations, and altered HOX expression

Antonio Faiella, Marius Wernig, G. Giacomo Consalez, Ute Hostick, Clementine Hofmann, Elisabeth Hustert, Edoardo Boncinelli, Rudi Balling, Joseph H. Nadeau

Research output: Contribution to journalArticlepeer-review

Abstract

Valproate (VPA) is one of several effective anti-epileptic and mood-stabilizing drugs, many of which are also potent teratogens in humans and several other mammalian species. Variable teratogenicity among inbred strains of laboratory mice suggests that genetic factors influence susceptibility. While studying the genetic basis for VPA teratogenicity in mice, we discovered that parental factors influence fetal susceptibility to induced malformations. Detailed examination of these malformations revealed that many were homeotic transformations. To test whether VPA, like retinoic acid (RA), alters HOX expression, pluripotent human embryonal carcinoma cells were treated with VPA or RA and Hox expression assessed. Altered expression of specific Hox genes may thus account for the homeotic transformations and other malformations found in VPA-treated fetuses.

Original languageEnglish
Pages (from-to)227-236
Number of pages10
JournalHuman Molecular Genetics
Volume9
Issue number2
Publication statusPublished - 2000

ASJC Scopus subject areas

  • Genetics

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