ProjectZebrafish as a Detector and Discriminator of Organophosphate Exposure
Project Leader: Elwood Linney
Publications ↓Project Description
Dr. Linney and his research team's working hypothesis is that there is a hierarchy of effects of organophosphate embryonic organophosphate exposure but selective targets and developmental windows are responsible for adult effects. They plan to use zebrafish to screen organophosphate pesticides to examine embryonic and larval effects upon exposure and in collaboration with the Levin laboratory, to investigate and compare effects of these exposures upon learning. Their intention is to screen at least 3 additional esterase inhibitors (along with chlorpyrifos: parathion, diazinon from the superfund list, and the non-superfund list but commonly used malathion). The four specific aims are:
- to perform dosage studies with selected transgenic lines for the first 5 days post-fertilization and to score for a)inhibition of acetylcholine esterase and b) morphological effects—preliminary behavioral differences will be noted for potential analysis of adults by E. Levin
- to perform 5 day time courses with selected exposures and to perform microarray analyses to identify genes, clusters of genes and time course of gene expression effects
- through analysis of expression work to a) identify potential unique genes (per chemical) that are markedly up-regulated (as candidate genes for isolating their promoters to create inhibitor-specific transgenic biosensor) and b) to identify potential genes and their time-course that are positively or negatively affected by the exposure to differentiate effects of different inhibitors and potentially identify pathways affected—this could include in situ localization of the genes affected by the exposure
- from specific aim 3) the generation of organophosphate-specific biosensor transgenic fish based upon unique genes up-regulated by each inhibitor, evaluate transgenics with inhibitor exposures and determine whether battery of transgenic fish can be used to assay mixtures of inhibitors.
Description ↑Publications
Roy, N.M. and Linney, E. 2008. Zebrafish as a model for studying adult effects of challenges to the embryonic nervous system. Chapter 14 in “Source Book of Models for Biomedical Research” edited by P. M. Conn, Humana Press, Inc. Totowa, NJ. (in press).
Lassiter, CS and Linney, E. 2007. Embryonic expression and steroid regulation of brain aromatase (cyp19a1b) in zebrafish (Danio rerio). Zebrafish. 4 49-57.
Cook J, Denslow ND, Iguchi T, Linney EA, Miracle A, Shaw JR, Viant MR, and Zacharewski TR. 2006. “Omic” approaches in the context of environmental toxicology. In Emerging Molecular and Computational Approaches for Cross-Species Extrapolations, Chapter 1. Soc of Env. Toxicology and Chemistry.
Linney, Elwood and Ava J. Udvadia. 2004. Construction and detection of fluorescent germline transgenic zebrafish. Chapter Vol. 254 in: Methods in Molecular Biology, 2004. Humana Press, Inc, Louisville, KY. pp.271-288.
Linney, Elwood, Lucia Upchurch, and Sue Donerly. 2004. Zebrafish as a neurotoxicological model. Neurotoxicology and Teratology. 26(6):709-718.
Levin, Edward, Elizabeth Chrysanthis, Kari Yacsin, and Elwood Linney. 2003. Chlorpyrifos exposure of developing zebrafish: effects on survival and long-term effects on response latency and spatial discrimination. Neurotoxicology and Teratology. 25(1):51-57.
Linney, Elwood and A.J. Udvadia. 2003. Construction and detection of fluorescent germ-line transgenic zebrafish. In: Methods in Molecular Medicine. (). Humana Press, (in press)
Udvadia, Ava J. and Elwood Linney. 2003. Windows into development: historic, current, and future perspectives on transgenic fish. Developmental Biology. 256(1):1-17.
Lassiter, Chris S., B. Kelley, and Elwood Linney. 2002. Genomic structure and embryonic expression of estrogen receptor beta a (ERBa) in zebrafish (Danio rerio). Gene. 299:141-151.