The main objective of this grant proposal is to use precision-cut tissues slices from genetically-modified mice as an in vitro system for rapid assessment for potential chemical toxicities. The Phase I goals are to develop two transgenic mice, one that has an aryl hydrocarbon receptor responsive promoter linked to green fluorescent protein and another that has an estrogen receptor responsive promoter linked to yellow fluorescent protein. These mice would facilitate the development of subsequent in vitro model systems to test the responsiveness of the constructed promoters to toxic chemicals. After characterization of these transgenic mice, the PI proposes in Phase II to crossbred these two transgenic strains containing the aforementioned reporter constructs to generate a supermouse. Tissues slices from this supermouse can be simultaneously monitored for a number of toxic events in multiple tissues from a single mouse. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE
Thesaurus Terms: Laboratory Mouse, Model Design /Development, Sectioning, Tissue /Cell Preparation, Toxicant Screening, Transgenic Animal Aromatic Hydrocarbon Receptor, Bioassay, Biological Model, Cytochrome P450, Estrogen, Green Fluorescent Protein
