Polymorphisms and functional differences in aryl hydrocarbon receptors (AhR) in Japanese field mice, Apodemus speciosus

Dioxins, which are unintentionally generated toxic pollutants, exert a variety of adverse effects on organisms. The majority of these effects, which include teratogenesis, immunosuppression, tumor promotion, and endocrine disruption, are mediated through aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor. Genetic variations in AhR result in different survivability under exposure to dioxin contamination, which might affect the genetic structure of wildlife populations through differential susceptibility to dioxin exposure. The aim of this study was to clarify the polymorphisms of AhR in Japanese field mice, Apodemus speciosus, and their functional differences in order to develop a molecular indicator for dioxin sensitivity. Wild Japanese field mice had abundant polymorphisms in AhR coding region. Seventy-one single nucleotide polymorphisms, 27 of which occur amino acid substitutions, and consequently 49 alleles were identified in 63 individuals. In the functional analysis of AhR variants using transient reporter assays, a Gln to Arg mutation at amino acid 799 exhibited a significant decrease in the level of transactivational properties (p = 0.015) which might modify the dioxin susceptibility of an individual. (C) 2010 Elsevier B.V. All rights reserved.