Changes in brain catecholamine metabolism in catechol-O-methyltransferase-deficient mice

Catechol-O-methyltransferase (COMT) is one of the main mammalian enzymes involved in the metabolism of catecholamines such as dopamine and norepinephrine. Catecholamine metabolism is important for regulating normal functioning of the nervous system, including emotions and stress responses. COMT activity in the nervous system allows animals with an inactive comt gene to be used as a model for studying mental disorders. We created a new line of mice with a knockout of the comt gene using CRISPR/Cas9 technology. The concentration of neurotransmitters and their metabolites in the striatum and prefrontal cortex of comt knockout and wild-type mice was measured by high-performance liquid chromatography using an internal standard 2,3-dihydroxybenzoic acid, which is not found in native tissue, at a concentration of 100 ng/ml. Homozygous comt knockout mice were found to have a lack of homovanillic acid, the end product of dopamine metabolism, in the prefrontal cortex and striatum, while levels of the intermediate product 3,4-dihydroxyphenylacetic acid were increased. Norepinephrine levels were increased in the prefrontal cortex of comt knockout mice, while no significant differences were found in the striatum between comt knockout and wild-type mice. Despite corresponding changes in catecholamine metabolites, serotonin and dopamine concentrations were not significantly different between comt knockout and wild-type mice.