Monogenic inheritance of catechol-O-methyltransferase activity in the rat-biochemical and genetic studies

Catechol-O-methyltransferase (COMT) activities in the livers and kidneys of Fischer-344 (F-344) inbred rats were only 58 and 59 per cent, respectively, of those in the same organs of inbred Wistar-Furth (W-F) rats. Breeding experiments were performed to study possible mechanisms of inheritance of COMT activity in these animals. COMT activities in livers and kidneys of F1 (hybrid) animals (N = 36) were intermediate between those of the parental strains, but were closer to W-F (N = 22) than to F-344 (N = 22) values. The results of studies of F2 generation (N = 147) and backcross (N = 171) animals were compatible with the autosomal recessive inheritance of low COMT activity. 25.8 per cent of the F2 animals fell into a "low" COMT group when enzyme activities in both liver and kidney were used for phenotypic classification. This result is compatible with autosomal recessive inheritance of the trait "low" COMT. Statistical estimates of the number of genes involved in the control of COMT activity in these rats were also compatible with monogenic inheritance. Because of the possibility that there might be genetically determined differences in the biochemical properties of COMT in F-344 and W-F rats, COMT activities in tissue homogenates of liver from the two strains were compared with regard to thermal stability, electrophoretic behaviour, apparent Michaelis-Menton (K_m) constant for substrates, and responses to three COMT inhibitors (tropolone, S-adenosyl-l-homocysteine, and calcium). No differences in thermal stability, R_f values after electrophoresis, apparent K_m values for substrates or 50 per cent inhibitory concentrations of the enzyme inhibitors for hepatic COMT were detected between the two strains of rats.