Abstract
The effect of a lack of the gene encoding monoamine oxidase A (MAO A) in transgenic Tg8 mice on the activity of tryptophan hydroxylase (TPH), the rate‐limiting enzyme in serotonin (5‐HT) biosynthesis, and on the levels of 5‐HT and 5‐hydroxyindoleacetic acid (5‐HIAA) in the midbrain, hypothalamus, hippocampus, striatum, amygdala, and frontal cortex was studied. It was shown that mice with a genetic MAO A knockout differed from mice of the initial C3H/HeJ strain in having a higher level of 5‐HT and a lower level of its metabolite, 5‐HIAA, in all brain regions but the frontal cortex, where the changes were insignificant. Although the 5‐HIAA/5‐HT ratio in various brain regions differed considerably, the decrease of the 5‐HT oxidative deamination index in Tg8 mice was similar in different brain regions (to 41–45% of control values), with the exception of the frontal cortex, where the decrease of the 5‐HIAA/5‐HT was somewhat smaller (to 54%). The presence of the remaining 45% ± 1.9% of the control ratio value indicates rather effective oxidative deamination of 5‐HT in MAO A knockout mice and explains the lack of severe behavioral and pathological consequences in MAO A genetic deficiency. An increase of TPH activity in mice lacking MAO A was found in the frontal cortex, hippocampus, and amygdala. No significant changes were found in the striatum, hypothalamus, and midbrain. The data show an effect of the MAO A gene mutation on TPH and indicate a uniform decrease of 5‐HT catabolism in different brain regions except for the frontal cortex, which is somewhat more resistant to the lack of MAO A than other brain structures. J. Neurosci. Res. 66:423–427, 2001. © 2001 Wiley‐Liss, Inc.