Research over the last decade has lead to biochemical characterization of the Ah-receptor, description of the structural requirements of receptor agonists and an initial understanding of the mechanism by which this protein activates gene expression. Today, a number of important questions remain, such as how does the Ah-receptor mediate the toxicity of planar halogenated aromatic hydrocarbons like TCDD, is the Ah-receptor evolutionarily and functionally related to members of the steroid thyroxin receptor superfamily, why do different species and murine strains display differing sensitivities to TCDD toxicity? To begin to answer these questions, we propose to clone the cDNAs which encode the Ah-receptor from a variety of murine strains and animal models which display marked differences in their sensitivity to TCDD toxicity. Upon cloning these genes, we then propose to map and characterize the functional domains involved in ligand and DNA binding, as well as interactions with other proteins, such as the 90 kDa heat shock protein. our cloning strategy is based upon the generation of a number of powerful new probes with which to identify this rare cDNA in a recombinant library. These probes include; 1) a number of oligonucleotide probes derived from receptor amino acid sequence data and 2) two antisera which recognize unique Ah-receptor epitopes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29ES005703-03
Application #
3465358
Study Section
Toxicology Subcommittee 2 (TOX)
Project Start
1991-08-01
Project End
1996-07-31
Budget Start
1993-08-01
Budget End
1994-07-31
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Type
Schools of Dentistry
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Perelis, Mark; Marcheva, Biliana; Ramsey, Kathryn Moynihan et al. (2015) Pancreatic ? cell enhancers regulate rhythmic transcription of genes controlling insulin secretion. Science 350:aac4250
Stevens, Emily A; Mezrich, Joshua D; Bradfield, Christopher A (2009) The aryl hydrocarbon receptor: a perspective on potential roles in the immune system. Immunology 127:299-311