Characterization of the CYP2C5 gene in 21L III/J rabbits. Allelic variation affects the expression of P450IIC5.

摘要: Rabbits exhibit two heritable phenotypes, 21L and 21H, with the latter displaying roughly 10-fold higher liver microsomal progesterone 21-hydroxylase activity. The activity of 21H animals reflects elevated expression cytochrome P-450 1 (P450IIC5). Breeding studies indicate that this phenotypic difference is linked to allelic CYP2C5 genes (Johnson, E. F., Finlayson, M., Husjsak, C. Pendurthi, U. R., Tukey, R. H. (1989) Arch. Biochem. Biophys. 273, 273-280). In study, we report on structure gene in inbred strain III/J. A cDNA encoding P450IIC5 was generated from III/J rabbit mRNA using polymerase chain reaction amplify sequence. DNA sequence analysis revealed encoded same protein as cloned previously a rabbit, demonstrating structural differences do not underlie exons surrounding intron regions genomic clones encode portions showed exon sequences were identical codon positions exon/intron junctions are conserved other class II genes. Southern blot digested BamHI probed portion isolated 5 characterized study an allele conferring phenotype. Primer extension P450IIC5-specific oligonucleotide demonstrated uses several transcriptional start sites both rabbits. Analysis livers rabbits greater than 20-fold relative abundance mRNA, which accounts quantitatively for