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2111432 
Journal Article 
Regulatory gene product of the Ah locus. Characterization of receptor mutants among mouse hepatoma clones 
Legraverend, C; Hannah, RR; Eisen, HJ; Owens, IS; Nebert, DW; Hankinson, O 
1982 
Yes 
Journal of Biological Chemistry
ISSN: 0021-9258
EISSN: 1083-351X 
257 
11 
6402-6407 
English 
6896205 
The major regulatory gene product of the Ah locus is a cytosolic receptor which binds avidly to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Ah receptor levels in the cytosol and accumulation of the inducer-receptor complex in the nucleus have been examined in the mouse hepatoma cell culture parent line Hepa-1c1c7 and in six mutant clones that exhibit varying degrees of deficiency in aryl hydrocarbon (benzo[a]pyrene) hydroxylase (EC 1.14.14.1) inducibility. One of these clones (c3) is dominant, whereas the others are known to be recessive and to belong to three distinct complementation groups (and, therefore, reflect mutations in three different genes): c1 and c5, c2 and c6, and c4. Clones c1, c3, and c5 have essentially normal Ah receptor levels, compared with the wild type Hepa-1c1c7 parent, possess normal kinetics for translocation of the inducer-receptor complex into the nucleus, and yet exhibit very low or nondetectable basal or inducible aryl hydrocarbon hydroxylase activity; these clones could represent a mutation in the P1-450 structural gene or other genes responsible for the induced hydroxylase activity. Clones c2 and c6 are receptor-deficient mutants, having no more than 10% of wild type Ah receptor levels, normal kinetics of nuclear translocation of the inducer-receptor complex, and no more than 20% of wild type hydroxylase inducibility by either TCDD or benzo[a]anthracene. The defect in c2 cells was shown by both in vitro and in vivo TCDD-binding studies not to reflect a lack of receptor saturability. Clone c4 has normal cytosolic levels of Ah receptor, is defective in nuclear translocation of the inducer-receptor complex, and lacks any detectable basal or inducible aryl hydrocarbon hydroxylase activity.