1. Sponsor Organization: NIH/NIEHS

2. Project Title: 05703-08 MOLECULAR CLONING OF AH RECEPTOR POLYMORPHS

3. Project Focus:

• Project Primary Focus: Exposure Assessment
• Project Secondary Focus:

4. Description:

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 donces 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 differees 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 sequenced data and 2) two antisera which recognize unique Ah-receptor epitopes.

5. References:

6. Inventory Category:

• Primary: Models
• Secondary:

7. Inventory Subcategory:

• Primary: Basic Research
• Secondary:

8. Keywords for Experimental System/Species:

• Species:
  • Mammal
  • Mouse
• Study Type:
  • Laboratory Study
• Fate and Transport:

9. Keywords for Experimental Endpoints:

• Health Effect:
• Hormonal Measures:
  • Ah Receptor
• Level Of Study:
  • Gene Expression
• Chemistry Metabolism:
• Life Stage:
• Risk Assessment:

10. Chemical Agents:

• Dioxins

11. Performing Institution:

• NORTHWESTERN UNIVERSITY

12. Contact:

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