Identification of Mouse CYP2C Involved in Arachidonic Acid

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AIMS To identify the CYP2Cs in the mouse, establish their contribution to the metabolism of endogenous compounds such as arachidonic acid and retinioic acid (Vitamin A) and to establish their contribution to the metabolism of drugs and environmental chemical such as those used in bioassays. To determine which tissues these enzymes are found in, and the importance of these changes in endogenous compounds in physiological and pathological processes process. Eventually specific knockout mice will be generated to test the importance of these pathways in physiology and their importance in the metabolism of enviromental chemicals. ACCOMPLISHMENTS We have identified five CYP2Cs in the mouse, including four new CYP2Cs. This is a common laboratory animal for toxicity and carcinogenicity tests. We expressed all five CYP2Cs in cDNA expression systems and compared their ability to metabolize arachidonic acid is being compared with that of the human forms. CYP2C29 was the predominant form and produced primarily 14,15 epoxyeicosatrienoic acid (EET). CYP2C29 mRNA was also found in lung, liver, brain, kidney, heart and intestine. CYP2C39 also producued 14,15 EET. CYP2C38 produced 1,12-EET mRNA was found in liver brain, kidney and intestine. CYP2C40 produced an unidentified hydroxyeicosatetraenoic acid (16, 17, or 18-HETE) and was also found in brain, kidney and intestine. The presence of some of these enzymes in extrahepatic tissues such as lung and colon suggests their importance in physiological roles in these organs.