Global Gene Expression Analysis Reveals Dynamic and Developmental Stage Dependent Enrichment of Lead (Pb)-Induced Neurological Gene Alterations
- Peterson, S.M., Zhang, J., Weber, G., and Freeman, J.L.
- Environmental health perspectives 119(5): 615-622 (Journal)
- Registered Authors
- Freeman, Jennifer, Peterson, Sam
- MeSH Terms
- Embryo, Nonmammalian/drug effects
- Gene Expression Profiling/methods*
- Gene Expression Regulation, Developmental/drug effects*
- 21147602 Full text @ Environ. Health Perspect.
Peterson, S.M., Zhang, J., Weber, G., and Freeman, J.L. (2011) Global Gene Expression Analysis Reveals Dynamic and Developmental Stage Dependent Enrichment of Lead (Pb)-Induced Neurological Gene Alterations. Environmental health perspectives. 119(5):615-622.
Background: The underlying genetic mechanisms specific to subtle neurological alterations associated with environmental Pb exposures have not been clearly elucidated. Objectives: The goal of this study was to identify novel gene targets and the underlying genetic mechanisms associated with developmental Pb neurotoxicity. Methods: Zebrafish embryos were exposed to a range of Pb concentrations throughout early development to establish relative toxicity. Zebrafish were then exposed to a sub-lethal dose of Pb immediately following fertilization through 72 or 120 hours post fertilization (hpf) and global gene expression was analyzed for molecular pathway and gene ontology enrichment. Western blot analysis was then performed to investigate the translation of gene expression changes to protein levels. Results: After 72 hpf, 231 probes representing 90 non-redundant genes with well established function or orthology to human genes were identified as being altered by Pb exposure. This gene set was both confirmatory and novel in nature and was highly enriched for neurological development, function and disease. Moreover, gene changes at this time point were correlated to altered protein levels. Alternatively, the gene set at 120 hpf did not share association with neurological development. Conclusions: Global gene expression alterations associated with developmental Pb exposure was dynamic and dependent on developmental stage. Gene expression alterations at the 72 hpf time point were highly enriched with genes and molecular pathways associated with neurological development and disease. Moreover, a number of novel targets were identified for future exploration into their role in the genetic mechanisms underlying Pb-induced neurological alterations.
Genes / Markers
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes