PMID- 7841657 OWN - NLM STAT- MEDLINE DCOM- 19950309 LR - 20191023 IS - 0890-6238 (Print) IS - 0890-6238 (Linking) VI - 8 IP - 5 DP - 1994 Sep-Oct TI - Preliminary evidence of phenytoin-induced alterations in embryonic gene expression in a mouse model. PG - 383-95 AB - SWV mouse embryos collected on gestational days (GD) 9:12 and 10:00 following chronic in utero exposure to teratogenic concentrations of phenytoin were utilized for in situ transcription studies of gene expression. The substrate cDNA obtained from the frozen embryo sections was amplified into radiolabelled antisense RNA (RT/aRNA) and used as a probe to screen a panel of 20 cDNA clones representing genes that are important regulators of craniofacial and neural development. The magnitude of alteration in gene expression following phenytoin treatment was determined densitometrically by changes in the hybridization intensity of the aRNA probes to the cDNA clones immobilized to the slot blots. We found that both Wnt-1 and the calcium channel gene were developmentally regulated, as their level of expression decreased significantly between the two collection times. Phenytoin treatment produced a significant downregulation in the level of expression for 25% of the genes examined in the GD 9:12 embryos, including the growth factors TGF-beta and NT3, the proto-oncogene Wnt-1, the nicotinic receptor, and the voltage sensitive calcium channel gene. Additional changes in the coordinate expression of several of the growth and transcription factors were observed at both gestational timepoints. The application of RT/aRNA technology has extended our appreciation of the normal patterns of gene expression during craniofacial and neural development, and provided the first demonstration of multiple coordinate changes in transcription patterns following teratogenic insult. FAU - Musselman, A C AU - Musselman AC AD - Department of Veterinary Anatomy and Public Health, College of Veterinary Medicine, Texas A&M University, College Station 77843-4458. FAU - Bennett, G D AU - Bennett GD FAU - Greer, K A AU - Greer KA FAU - Eberwine, J H AU - Eberwine JH FAU - Finnell, R H AU - Finnell RH LA - eng GR - DE 11303/DE/NIDCR NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Reprod Toxicol JT - Reproductive toxicology (Elmsford, N.Y.) JID - 8803591 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Calcium Channels) RN - 0 (Ciliary Neurotrophic Factor) RN - 0 (DNA, Complementary) RN - 0 (Nerve Growth Factors) RN - 0 (Nerve Tissue Proteins) RN - 0 (Neurotrophin 3) RN - 0 (Proto-Oncogene Proteins) RN - 0 (RNA, Antisense) RN - 0 (Receptors, Nicotinic) RN - 0 (Transforming Growth Factor beta) RN - 6158TKW0C5 (Phenytoin) SB - IM GS - BDNF GS - CTNF GS - IGF GS - NGF GS - NT3 GS - TGF GS - Wnt-1 GS - c-fos GS - c-jun GS - creb GS - trk MH - Analysis of Variance MH - Animals MH - Brain-Derived Neurotrophic Factor MH - Calcium Channels/drug effects MH - Ciliary Neurotrophic Factor MH - Cloning, Molecular MH - DNA, Complementary/genetics MH - Disease Models, Animal MH - Down-Regulation MH - Embryonic and Fetal Development/drug effects/genetics MH - Female MH - Gene Expression Regulation, Developmental/*drug effects/genetics MH - Genes MH - Gestational Age MH - Mice MH - Nerve Growth Factors/drug effects/genetics MH - Nerve Tissue Proteins/drug effects/genetics MH - Neurotrophin 3 MH - Nucleic Acid Hybridization MH - Phenytoin/administration & dosage/*toxicity MH - Pregnancy MH - Proto-Oncogene Proteins/drug effects/metabolism MH - RNA, Antisense/genetics MH - Receptors, Nicotinic/drug effects/genetics MH - Transcription, Genetic/drug effects/genetics MH - Transforming Growth Factor beta/drug effects/genetics EDAT- 1994/09/01 00:00 MHDA- 1994/09/01 00:01 CRDT- 1994/09/01 00:00 PHST- 1994/09/01 00:00 [pubmed] PHST- 1994/09/01 00:01 [medline] PHST- 1994/09/01 00:00 [entrez] AID - 10.1016/0890-6238(94)90078-7 [doi] PST - ppublish SO - Reprod Toxicol. 1994 Sep-Oct;8(5):383-95. doi: 10.1016/0890-6238(94)90078-7.