Genetic polymorphisms for a phenobarbital-inducible cytochrome P-450 map to the Coh locus in mice.
Southern blot analysis suggests that multiple sequences homologous to a phenobarbital-inducible cytochrome P-450 cDNA are present in the rat and mouse genomes. A cDNA (pP-450b-5) to a major phenobarbital-inducible cytochrome P-450 mRNA species in the rat detected 6 polymorphic DNA fragments when hybridized to DNA from C57BL/6J and DBA/2J mice restricted with endonucleases EcoRI, BamHI, and PvuII. Using the BXD recombinant inbred strains, five of these polymorphisms were mapped to the Coh (coumarin hydroxylase) locus on chromosome 7 of the mouse. The Coh locus has previously been shown to code for a phenobarbital-inducible enzyme, believed to be a cytochrome P-450, which catalyzes the conversion of coumarin to 7-hydroxycoumarin (umbelliferone). The DNA polymorphisms appear to reflect changes in either cytochrome P-450 genes or pseudogenes that are very closely linked to the gene responsible for differential coumarin hydroxylase in mice or it may represent a change(s) in the Coh gene itself. The region of the Coh locus on chromosome 7 may be the site of a cluster of cytochrome P-450 genes.
D000818:Animals; D002874:Chromosome Mapping; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004247:DNA / Q000032:analysis; D004262:DNA Restriction Enzymes / Q000378:metabolism; D015246:Deoxyribonuclease EcoRI; D015247:Deoxyribonuclease HindIII; D004790:Enzyme Induction; D007527:Isoenzymes / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D010634:Phenobarbital / Q000494:pharmacology*; D011110:Polymorphism, Genetic; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains
D007527:Isoenzymes; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D004262:DNA Restriction Enzymes; D015246:Deoxyribonuclease EcoRI; D015247:Deoxyribonuclease HindIII; D010634:Phenobarbital