Each year, approximately 120,000 babies are born in the US with a major birth defect and genetic and environmental factors play an important role. Embryonic differentiation pathways are highly conserved among vertebrates. The Xenopus laevis embryo is an established toxicology model with ease of chemical exposure. Inter-laboratory studies demonstrated the reliability of the Frog Embryo Teratogenesis Assay-Xenopus (FETAX). Xenopus microarray analysis holds great promise as a versatile tool for drug screening and mechanistic studies of environmental toxicology. Our long-term goal is to develop Xenopus microarrays, categorize environmental toxicants according to their gene expression profiles and discover markers of environmental contaminants. About 18,500 EST clones were obtained from NIEHS. Initial studies completed in the Phase I with about1,200 clones demonstrate the feasibility of using Xenopus microarrays to identify genes responsive to phorbol 12-myristate 13-acetate (PMA) in early embryogenesis. In the Phase II, we will develop high-density cDNA microarrays and identify genes regulated by 7 classes of toxicants. These results will be utilized to produce diagnostic subarrays. We will also produce interspecies extrapolation chips to study conservation of gene regulation by toxicants. In addition, the feasibility of use of X. laevis chips for a X. tropicalis genetic manipulation study will be explored.
