Isolation of a new canine cytochrome P450 CDNA from the cytochrome P450 2C subfamily (CYP2C41) and evidence for polymorphic differences in its expression.

Two members of the canine cytochrome P4502C subfamily [CYP2C21 and CYP2C41 (sequence has been submitted to Genbank with accession number AF016248)] were cloned from three beagle liver cDNA libraries. The two canine CYP2C cDNAs exhibited 70% nucleotide and amino acid identity as well as 74-83% nucleotide and 67-76% amino acid identity with the human CYP2Cs. Canine CYP2C41 is more homologous to the human CYP2Cs than CYP2C21. The two canine CYP2C cDNAs exhibited a slightly lower nucleotide and amino acid identity (66-77%) with the rat P450CYPs, 2C11 and 2C12. Reverse transcription-polymerase chain reaction-based restriction enzyme tests for CYP2C21 and 2C41 mRNAs as well as polymerase chain reaction-based tests for genomic DNA were developed. CYP2C21 cDNA was present in the livers of all dogs tested (N = 9), but CYP2C41 was present in only 1 of the 9 (11%). Genomic tests found that the gene coding for CYP2C21 was also present in all dogs tested (N = 25), of which 15 were beagles and 10 mixed breeds. In contrast, the gene coding for CYP2C41 was present in only 16% (4 out of 25) of the dogs. An even distribution of the CYP2C41 gene was found between the sexes and between beagles and mixed breeds. This unique polymorphism in the canine CYP2C subfamily may be a source of variability in the metabolic clearance in dogs of xenobiotics that are metabolized by the cytochrome P450 2C subfamily of enzymes.