Transgenic fish will be used to study the effect of pesticides upon gene expression of transgenic reporter genes that report changes in the estrogen-responsive, retinoic acid-responsive pathways in developing fish and in the development of the nervous system. Our hypothesis are: 1) Liver reporter transgenic fish embryos and larvae can be used as biosensors to detect whole organism effects of environmental toxicants. 2) There may be unique windows of sensitivity of chemicals which impact upon the estrogen receptor signal transduction pathway that can be detected and evaluated in fish models. 3) Dicistronic reporter genes will allow for both tissue specific expression studies plus quantitative evaluation of toxicants upon whole fish embryos. 4) Transgenic techniques developed for the zebrafish can be used for indigenous species such as the killifish, Fundulus heteroclitus.
The specific aims of this proposal are: I. To explore the use of transgenic zebrafish models to screen several superfund chemicals for detectable differences of GFP expression. II. To examine the behavior and incorporation of the GFP positive primordial germ cells into the developing reproductive tract and to see if there are biological effects upon sexual determination of the fish through treatment with pesticides investigated in specific aim I. III. To develop dicistronic vectors for the appropriate transgenic promoters that will allow for ligand inducible expression of both a luciferase gene (for quantitative measurement) and a GFP gene (for anatomical localization of signal). IV. To develop Fundulus models with the most appropriate transgenes based upon the results of specific aims I and II.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
1P42ES010356-01
Application #
6323875
Study Section
Special Emphasis Panel (ZES1-DPB-D (G3))
Project Start
2000-06-01
Project End
2005-03-31
Budget Start
Budget End
Support Year
1
Fiscal Year
2000
Total Cost
$86,441
Indirect Cost
Name
Duke University
Department
Type
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705
Meyer, Joel N; Hartman, Jessica H; Mello, Danielle F (2018) Mitochondrial Toxicity. Toxicol Sci 162:15-23
Oliveri, Anthony N; Ortiz, Erica; Levin, Edward D (2018) Developmental exposure to an organophosphate flame retardant alters later behavioral responses to dopamine antagonism in zebrafish larvae. Neurotoxicol Teratol 67:25-30
Slotkin, Theodore A; Skavicus, Samantha; Seidler, Frederic J (2018) Developmental neurotoxicity resulting from pharmacotherapy of preterm labor, modeled in vitro: Terbutaline and dexamethasone, separately and together. Toxicology 400-401:57-64
Lefèvre, Emilie; Bossa, Nathan; Gardner, Courtney M et al. (2018) Biochar and activated carbon act as promising amendments for promoting the microbial debromination of tetrabromobisphenol A. Water Res 128:102-110
Kollitz, Erin M; Kassotis, Christopher D; Hoffman, Kate et al. (2018) Chemical Mixtures Isolated from House Dust Disrupt Thyroid Receptor ? Signaling. Environ Sci Technol :
Hartman, Jessica H; Smith, Latasha L; Gordon, Kacy L et al. (2018) Swimming Exercise and Transient Food Deprivation in Caenorhabditis elegans Promote Mitochondrial Maintenance and Protect Against Chemical-Induced Mitotoxicity. Sci Rep 8:8359
Luz, Anthony L; Kassotis, Christopher D; Stapleton, Heather M et al. (2018) The high-production volume fungicide pyraclostrobin induces triglyceride accumulation associated with mitochondrial dysfunction, and promotes adipocyte differentiation independent of PPAR? activation, in 3T3-L1 cells. Toxicology 393:150-159
Day, D B; Xiang, J; Mo, J et al. (2018) Combined use of an electrostatic precipitator and a high-efficiency particulate air filter in building ventilation systems: Effects on cardiorespiratory health indicators in healthy adults. Indoor Air 28:360-372
Slotkin, Theodore A; Ko, Ashley; Seidler, Frederic J (2018) Does growth impairment underlie the adverse effects of dexamethasone on development of noradrenergic systems? Toxicology 408:11-21
Rock, Kylie D; Horman, Brian; Phillips, Allison L et al. (2018) EDC IMPACT: Molecular effects of developmental FM 550 exposure in Wistar rat placenta and fetal forebrain. Endocr Connect 7:305-324

Showing the most recent 10 out of 291 publications