Linked Life Data

9098922

Source:http://linkedlifedata.com/resource/pubmed/id/9098922

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1997-6-6
pubmed:abstractText
The teratogenic potential of valproic acid has been well established both in experimental models and in human clinical studies. As with all human teratogens, there are genetically determined differences in individual susceptibility to the induction of congenital defects. Using a mouse model of valproate-induced neural tube defects, a study was undertaken to examine differential changes in gene expression for selected transcription factor (Pax-3, Emx-1, Emx-2, c-fos, c-jun, creb) and cell cycle checkpoint genes (bcl-2, p53, wee-1) during neural tube closure. In general, exposure to teratogenic concentrations of valproic acid elicited GD 9:12 control levels of transcription factor mRNA expression in GD 9:0 embryos of both strains. This accelerated developmental profile is marked by significant elevation of Emx-1, Emx-2, c-fos, c-jun, and creb expression. There was also a significant over expression of the cell cycle genes p53 and bcl-2 in the LM/Bc embryos in response to the teratogenic insult. Examination of the ratio of expression of these genes clearly favored bcl-2, which supports the hypothesis that altered neuroepithelial cell proliferation rates, rather than increased apoptosis, is the underlying mechanism by which valproic acid alters normal neural tube morphogenesis. An investigation into interactive effects of these genes on the molecular profile of GD 9:0 embryos further validated this observation. That is, the overall proliferative state among the control embryos was prematurely modified into a more differentiated state following teratogenic insult. These results suggest that alterations in the expression of multiple genes are most likely responsible for valproic acid-induced neural tube defects.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0040-3709
pubmed:author
pubmed:issnType
Print
pubmed:volume
54
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
284-97
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Valproic acid-induced changes in gene expression during neurulation in a mouse model.
pubmed:affiliation
National Veterinary Research Institute, Department of Pharmacology and Toxicology, Pulawy, Poland.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.