Identification of constitutive androstane receptor cDNA in northern fur seal (Callorhinus ursinus).

Constitutive androstane receptor (CAR) plays a key role in the transcriptional regulation of CYP2B, 2C and 3A genes in response to phenobarbital, ortho-chlorine substituted polychlorinated biphenyls (PCBs) and sex steroids in rodents and human. However, studies addressing CAR are limited to certain laboratory animals and cell lines, and there is little information on the presence of CAR and its physiological and contaminant-related functions in wildlife. While aquatic mammals including seal species are at the top of food chain and highly contaminated by xenochemicals such as PCBs, induction of CYP2/3 subfamilies by such chemical exposure and their regulatory mechanisms have not yet been established in these animals. To investigate mechanisms of CAR-CYPs signaling pathways in aquatic mammals, we initially attempted to isolate CAR cDNA in the liver of northern fur seals (Callorhinus ursinus) from off-Sanriku, Japan. The full-length CAR cDNA had an open reading frame of 1047 bp that encodes a protein containing 348 amino acids. Comparison of the amino acid sequence of CAR from the fur seal with those from other mammalian species showed high identities with CARs from human (83%), monkey (82%), rat (76%) and mouse (73%), revealing a conservation of CAR among the mammalian species. Phylogenetic analysis demonstrated that the fur seal CAR was classified into CAR clade and not into PXR/BXR or VDR clade, suggesting the CARs would be conserved among divergent mammals including aquatic species. With our concomitant paper, where CAR cDNA isolation from the liver of Baikal seal is reported (Iwata et al., in preparation), to our knowledge, this is the first study on the identification of CAR cDNA from wildlife species.