The murine Ah locus: a new allele and mapping to chromosome 12

The Ah locus in mice, the presumed structural gene for the Ah receptor, is polymorphic in mice: some inbred strains carrying the Ahb allele express a high affinity receptor and are sensitive to receptor agonists, while other strains carrying the Ahd allele express a lower affinity receptor and are less sensitive to agonists. Using the photoaffinity ligand for the Ah receptor, [125I]-2-azido-3-iodo-7,8-dibromodibenzo-p-dioxin, we have identified two allelic forms of the high affinity receptor (Ahb). In mouse strains of the C57 and C58 family and MA/MyJ, the photoaffinity labeled peptide in hepatic cytosol has an apparent molecular mass of 95 kDa (Ahb-1 allele), whereas in other responsive strains (e.g., C3H/HeJ, BALB/cByJ, A/J) the labeled peptide has an apparent mass of 104 kDa (Ahb-2 allele). In genetic crosses and backcrosses between C57BL/6J and C3H/HeJ mice, the expression of these peptides is consistent with codominant inheritance of two alleles at a single locus. From Scatchard plots of the specific binding of the reversible ligand, [3H]-2,3,7,8-tetrachlorodibenzo-p-dioxin, to hepatic cytosol, most strains of mice with the Ahb-1 allele were found to have an Ah receptor with a binding affinity, KD, of 0.4-0.7 nM, and a receptor concentration of 130-160 fmol/mg of protein, whereas most strains carrying the Ahb-2 allele have a slightly lower receptor affinity, KD = 0.8-1.3 nM, and a slightly lower receptor concentration, 80-110 fmol/mg of protein. From analysis of the strain distribution pattern of the Ahb-1 and Ahb-2 alleles in recombinant inbred strains, the Ah locus was linked to several unmapped loci (H-17, H-38, Ltw-2, Ly-18, D1Nyul, D1Nyu2), and this entire group mapped to chromosome 12.