PMID: 9188671Jun 13, 1997Paper

Strain-dependent alterations in the expression of folate pathway genes following teratogenic exposure to valproic acid in a mouse model

American Journal of Medical Genetics
R H FinnellG D Bennett

Abstract

The molecular basis for the well-established hierarchy of susceptibility to valproic acid-induced neural tube defects in inbred mouse strains was examined using in situ transcription and anti-sense RNA amplification methodologies with both univariate and multivariate analyses of the resulting gene expression data. The highly sensitive SWV strain demonstrated a significant reduction in the expression of the folate binding protein (FBP-1) following the teratogenic insult at gestational day 8:18, while the more resistant LM/Bc embryos were up-regulating this gene in response to valproic acid treatment. More importantly, at all 3 gestational timepoints spanning the period of murine neural tube closure examined in this study, the LM/Bc embryos had significantly higher MTHFR (5,10-methylenetetrahydrofolate reductase) gene expression levels compared to the SWV embryos. As this folate pathway enzyme is important in homocysteine and methionine metabolism, it suggests that the SWV embryos may be hypomethylated, and essential gene expression during critical periods of neural tube closure is compromised by the teratogenic exposure to valproic acid. This study represents the first evidence of a strain difference in transcriptional activity ...Continue Reading

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Citations

Nov 24, 1999·Clinical Genetics·J C DeanP D Turnpenny
Oct 24, 2007·European Journal of Medical Genetics·Usha KiniUNKNOWN Liverpool Manchester Neurodevelopmental Study Group
Aug 26, 2004·Congenital Anomalies·Padmanabhan Rengasamy, Rajagopala Ramanan Padmanabhan
May 7, 2004·The European Journal of Neuroscience·Akiko IchinoheKohji Sato
Jun 7, 2003·Epilepsia·Richard H FinnellOfer Spiegelstein
Mar 6, 1998·Critical Reviews in Oral Biology and Medicine : an Official Publication of the American Association of Oral Biologists·R H FinnellJ A Piedrahita
Jan 1, 2003·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Hirotomo SaitsuKohei Shiota
Feb 8, 2007·CNS Drugs·Michael W Mann, Gerard Pons

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