Increased susceptibility to retinoid-induced teratogenesis in TGF-beta2 knockout mice.
Transforming growth factor-beta (TGF-beta) and retinoic acid (RA) have been implicated in normal and abnormal embryonic development. The aim of this study was to investigate the effect of TGF-beta2 gene deletion on susceptibility to RA-induced teratogenesis in a mouse model. TGF-beta2 heterozygous or wild-type mice were mated and the dams dosed with a teratogenic dose of RA, or with control vehicle. The incidence of RA-induced cleft palate (CP) was 48% in wild-type embryos from wild-type dams, increasing to 71% in TGF-beta2 heterozygous littermates. Wild-type and TGF-beta2 heterozygous embryos from heterozygous dams exhibited a CP incidence of 74 and 77% respectively, following treatment with RA. Ninety-one percent of littermates nullizygous for TGF-beta2 were dead when examined; the remainder exhibited a CP. We conclude that the genotype of the dam and embryo with respect to TGF-beta2 affects the incidence of RA-induced teratogenesis.
Nugent
Paul
P
Birth Defects Center, University of Louisville School of Dentistry, 501 S Preston Street, Suite 301, Louisville, KY 40292, USA.
Pisano
Michele M
MM
Weinrich
Martin C
MC
Greene
Robert M
RM
D000014:Abnormalities, Drug-Induced; D000818:Animals; D002972:Cleft Palate / Q000139:chemically induced; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D013723:Teratogens / Q000633:toxicity*; D016212:Transforming Growth Factor beta / Q000172:deficiency / Q000235:genetics*; D053781:Transforming Growth Factor beta2; D014212:Tretinoin / Q000633:toxicity*
D013723:Teratogens; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D014212:Tretinoin