J. Biol. Chem., Vol. 258, Issue 16, 9585-9588, 08, 1983
Genetic polymorphisms for a phenobarbital-inducible cytochrome P-450 map to the Coh locus in mice
DL Simmons and CB Kasper
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.