Enhancer elements in the mouse CYP1A2 gene: A comparative sequencing among different inbred mouse strains

• Published in: Mutation research Vol. 632; no. 1; pp. 99 - 103
• Main Authors: Mikhailova, Olga N., Gulyaeva, Lyudmila F., Filipenko, Maxim L., Kaledin, Vasily I.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15-08-2007
• Subjects: 5′-Upstream region; Animals; Base Sequence; Cytochrome P-450 CYP1A2 - genetics; Cytochrome P450 CYP1A2; Enhancer Elements, Genetic; Genetic Variation; Inbred mouse strains; Male; Mice; Mice, Inbred AKR; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Inbred DBA; Mice, Inbred Strains - genetics; Molecular Sequence Data; MROD activity; Polymorphism; Sequence Analysis, DNA; 5′-Upstream region; MROD activity; Cytochrome P450 CYP1A2; Inbred mouse strains; Polymorphism
• ISSN: 1383-5718; 0027-5107; 1879-3592
• DOI: 10.1016/j.mrgentox.2007.04.013

CYP1A2 expression is constitutively high in mouse liver and is well known for metabolizing several drugs and many procarcinogens to reactive intermediates that can cause toxicity or cancer. In the present study, the basal level of hepatic CYP1A2 activity was shown to vary among different inbred mouse strains. The highest methoxyresorufin-
O-demethylase activity (261
±
52
pmol/mg
protein/min) was registered in CC57BR and the lowest (82
±
11
pmol/mg
protein/min) in C3H/a. We have tested the hypothesis that possible polymorphisms in regulatory elements in the 5′-upstream region of the mouse
CYP1A2 gene could cause the differences in CYP1A2 enzyme activity among different inbred strains. We have performed a study on the
CYP1A2 gene by sequencing the regulatory region from −4675 to −4204 where two enhancer elements were recently identified. The absence of mutation prescribing the phenotype in the
CYP1A2 gene was found. The region studied seems to be a highly conserved in mice and not to be associated with interstrain differences in constitutive CYP1A2 enzyme activity.