{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T20:50:43Z","timestamp":1761511843059,"version":"build-2065373602"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2003,7,22]],"date-time":"2003-07-22T00:00:00Z","timestamp":1058832000000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2003,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Catechol\u2010<jats:italic>O<\/jats:italic>\u2010methyltransferase (COMT) enzyme is a widely distributed enzyme that catalyses <jats:italic>O<\/jats:italic>\u2010methylation of catecholamines and other compounds having a catechol structure. Because there has been some concern about the consequences of a low COMT activity in the development of oestrogen\u2010dependent cancers and because one of the COMT inhibitors, tolcapone, has caused serious liver injuries in Parkinsonian patients, the histopathology and clinical chemistry of <jats:italic>Comt<\/jats:italic>\u2010gene\u2010disrupted mice were studied at the age of 12 months. Owing to the high COMT activities in liver and kidney and the role of COMT in the metabolism of catechol oestrogens, special emphasis was given to the histology of the liver, kidney and oestrogen\u2010dependent organs such as mammary glands and uterus.<\/jats:p><jats:p>The mice of both heterozygous and homozygous genotypes appear to be physically healthy and fertile. Diurnal motility rhythm and behaviour in measuring anxiety and depression were equal in all genotypes. At the age of 12 months, the body weight of homozygous mice was 7\u20139% lower than that of the other groups. This was re\ufb02ected in histology as a diminished incidence of vacuolation of liver cells (fatty change). Macroscopic pathology and histopathology revealed no abnormal \ufb01ndings in any COMT genotype. The values of some clinical chemistry parameters, such as alkaline phosphatase, alanine aminotransferase, urea, glucose, calcium and proteins, were at a higher level in homozygous animals compared with the wild\u2010type mice. However, all the values remained within the normal physiological range, and the differences in enzyme levels between genotypes were not re\ufb02ected as histopathological \ufb01ndings in the relevant organs. No changes in haematological parameters or plasma catecholamine concentrations were noted but plasma 3,4\u2010dihydroxyphenylethylene glycol levels were high in COMT null mice.<\/jats:p><jats:p>The results suggest that the full or 50% lack of <jats:italic>Comt<\/jats:italic> gene as such is not associated with any toxic consequences. 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