Poland A, Glover E, Taylor B A
McArdle Laboratory for Cancer Research, University of Wisconsin, Madison 53706.
Mol Pharmacol. 1987 Oct;32(4):471-8.
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.
小鼠中的Ah基因座，即假定的Ah受体结构基因，在小鼠中具有多态性：一些携带Ahb等位基因的近交系表达高亲和力受体，对受体激动剂敏感，而其他携带Ahd等位基因的品系表达较低亲和力受体，对激动剂不太敏感。使用Ah受体的光亲和配体[125I]-2-叠氮基-3-碘-7,8-二溴二苯并-对-二恶英，我们鉴定出了高亲和力受体（Ahb）的两种等位基因形式。在C57和C58家族以及MA/MyJ的小鼠品系中，肝细胞溶质中的光亲和标记肽的表观分子量为95 kDa（Ahb-1等位基因），而在其他反应性品系（如C3H/HeJ、BALB/cByJ、A/J）中，标记肽的表观分子量为104 kDa（Ahb-2等位基因）。在C57BL/6J和C3H/HeJ小鼠之间的遗传杂交和回交中，这些肽的表达与单个基因座上两个等位基因的共显性遗传一致。根据可逆配体[3H]-2,3,7,8-四氯二苯并-对-二恶英与肝细胞溶质特异性结合的Scatchard图，发现大多数具有Ahb-1等位基因的小鼠品系的Ah受体结合亲和力KD为0.4 - 0.7 nM，受体浓度为130 - 160 fmol/mg蛋白质，而大多数携带Ahb-2等位基因的品系的受体亲和力略低，KD = 0.8 - 1.3 nM，受体浓度略低，为80 - 110 fmol/mg蛋白质。通过分析重组近交系中Ahb-1和Ahb-2等位基因的品系分布模式，Ah基因座与几个未定位的基因座（H-17、H-38、Ltw-2、Ly-18、D1Nyul、D1Nyu2）连锁，并且这整个基因群定位于12号染色体。
