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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2005-6-21
pubmed:abstractText
Gene expression arrays reveal the potential linkage of altered gene expression with specific adverse effects leading to disease phenotypes. But how closely do microarray data reflect early physiological or pharmacological measures that predict toxic event(s)? To explore this issue, we have undertaken experiments in early mouse embryos exposed to various teratogens during neurulation stages with the aim of correlating large-scale changes in gene expression across the critical period during exposure. This study reports some of the large-scale changes in gene expression that can be detected in the optic rudiment of the developing mouse and rat embryo across the window of development during which the eye is exceedingly sensitive to teratogen-induced micro-/anophthalmia. Microarray analysis was performed on RNA from the headfold or ocular region at the optic vesicle and optic cup stages when the ocular primordium is enriched for Pax-6, a master control gene for eye morphogenesis. Statistical selection of differentially regulated genes and various clustering techniques identified groups of genes in upward or downward trajectories in the normal optic primordium during early eye development in mouse and rat species. We identified 165 genes with significant differential expression during eye development, and a smaller subset of 58 genes that showed a tight correlation between mouse-rat development. Significantly over-represented functional categories included fatty acid metabolism (up-regulated) and glycolysis (down-regulated). From studies such as these that benchmark large-scale gene expression during normal embryonic development, we may be able to identify the panel of biomarkers that best correlate with species differences and the risks for developmental toxicity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0041-008X
pubmed:author
pubmed:issnType
Print
pubmed:day
7
pubmed:volume
206
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
219-28
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Searching for biomarkers of developmental toxicity with microarrays: normal eye morphogenesis in rodent embryos.
pubmed:affiliation
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural