Tissue histopathology, clinical chemistry and behaviour of adult comt-gene-disrupted mice
Version of Record online: 22 JUL 2003
Copyright © 2003 John Wiley & Sons, Ltd.
Journal of Applied Toxicology
Volume 23, Issue 4, pages 213–219, July/August 2003
How to Cite
Haasio, K., Huotari, M., Nissinen, E. and Männistö, P. T. (2003), Tissue histopathology, clinical chemistry and behaviour of adult comt-gene-disrupted mice. J. Appl. Toxicol., 23: 213–219. doi: 10.1002/jat.909
- Issue online: 22 JUL 2003
- Version of Record online: 22 JUL 2003
- Manuscript Accepted: 24 MAR 2003
- Manuscript Revised: 20 MAR 2003
- Manuscript Received: 22 JAN 2003
- COMT-deﬁcient mice;
- COMT inhibition;
- COMT inhibitors
Catechol-O-methyltransferase (COMT) enzyme is a widely distributed enzyme that catalyses O-methylation 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-dependent cancers and because one of the COMT inhibitors, tolcapone, has caused serious liver injuries in Parkinsonian patients, the histopathology and clinical chemistry of Comt-gene-disrupted 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-dependent organs such as mammary glands and uterus.
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 7–9% lower than that of the other groups. This was reﬂected in histology as a diminished incidence of vacuolation of liver cells (fatty change). Macroscopic pathology and histopathology revealed no abnormal ﬁndings 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-type mice. However, all the values remained within the normal physiological range, and the differences in enzyme levels between genotypes were not reﬂected as histopathological ﬁndings in the relevant organs. No changes in haematological parameters or plasma catecholamine concentrations were noted but plasma 3,4-dihydroxyphenylethylene glycol levels were high in COMT null mice.
The results suggest that the full or 50% lack of Comt gene as such is not associated with any toxic consequences. Copyright © 2003 John Wiley & Sons, Ltd.