title: Developmental Toxicity of the Mouse Embryo (DTME)
status: Public on Mar 11 2004
contact.city: Louisville
contact.first: Thomas
contact.middle: B
contact.last: Knudsen
contact.email: singh.amarv@epamail.epa.gov
contact.state: KY
contact.address: 501 S Preston St
contact.department: Birth Defects Center
contact.country: USA
contact.web_link: http://systemsanalysis.louisville.edu/
contact.institute: University of Louisville
contact.phone: 502-852-4128
organism: Mus musculus
description: Developmental Toxicity of the Mouse Embryo (DTME) includes expression data from early embryos at risk for teratogen-induced eye malformations. Early mouse embryos were exposed to various teratogens during neurulation stages with the aim of correlating large-scale changes in gene expression with a generic histopathological biomarker (p53 protein induction) across the critical period during exposure, and with the risk of malformations in term fetuses (the various exposure scenarios produce ~10% risk of malformations in term fetuses averaged across 50 conditions of the experiment). Microarray analysis was performed on RNA from the embryo, prosencephalon, or headfold. Each condition for microarray analysis was replicated with independent sampling and reversal of labeling assignments (100 samples total). DTME compares genes expressed between test vs. reference samples as evidenced by data from two-channel MICROMAX system from PerkinElmer Life Sciences (Wellesley, MA 02481-4078, USA). It also includes a series of comparisons of early optic development in the optic primordium from mouse and rat embryos harvested at equivalent morphogenetic stages. The microarray platform uses a novel integrative chemistry that culminates massive signal amplification and greatly enhanced detection. The method incorporates unique two-channel indirect labeling of target RNA products with biotinyl-11-dCTP and fluorescein-12-dCTP (or dinitrophenol-11-dCTP) with post-hybridization amplification through conventional immunodetection and tyramide signal amplification. The probe was spotted with 2.4K sequence-verified human gene elements (single or duplicate) from 50 different cDNA libraries and positive- and negative- control genes. The cDNAs represent more than 10 different tissue sources: 80% brain-derived and more than 40% full-length cDNA sequences and a range of human diseases, metabolic, and regulatory pathways. The probe has been shown effective with target RNA from human, mouse, or rat biosources. The dataset includes "absolute" and "relative" values. Absolute values represent the background-corrected signal. For single-spot 2400 arrays this means one measurement for every spotted element and each color channel. Relative values represent ratiometric data normalized as follows: transformation to log2-space; lowess correction of MxA plot; internal standardization by mean absolute deviation; and normalization between replica pairs in each condition.
  Keywords = mouse
  Keywords = embryo
  Keywords = teratogen
  Keywords = toxicity
  Keywords = development
  Keywords = eye