TY - JOUR
T1 - A mouse model for valproate teratogenicity
T2 - Parental effects, homeotic transformations, and altered HOX expression
AU - Faiella, Antonio
AU - Wernig, Marius
AU - Consalez, G. Giacomo
AU - Hostick, Ute
AU - Hofmann, Clementine
AU - Hustert, Elisabeth
AU - Boncinelli, Edoardo
AU - Balling, Rudi
AU - Nadeau, Joseph H.
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
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M3 - Article
C2 - 10607833
AN - SCOPUS:0033968253
VL - 9
SP - 227
EP - 236
JO - Human Molecular Genetics
JF - Human Molecular Genetics
SN - 0964-6906
IS - 2
ER -