Cloning, after cloning, knock-out mice, and physiological functions of MAO A and B.

Cloning of MAO A and B has demonstrated clearly that MAO A and B are coded by different proteins with 70% amino acid identity. With the MAO A and B cDNA clones, we showed the tissue distribution and genomic structure of MAO A and B, the latter suggesting that they are derived from the same ancestral gene. The active sites, the role of cysteine residues, the three-dimensional models and the mitochondria targeting domains of both isoenzymes have been established. The transcriptional regulation of MAO A and B has been studied. MAO A KO mice showed increased levels of serotonin (5-HT), norepinephrine (NE), dopamine (DA) whereas MAO B KO mice showed increased phenylethylamine (PEA) levels only. Both MAO A and B KO mice showed increased response to stress. MAO A KO mice showed increased emotional learning and memory and aggressive behavior, but the vesicular monoamine transporter (VMAT2), 5-HT1A, 5-HT2A and 5-HT2C receptors were down regulated. 5-HT2A antagonist, ketanserin and MDL100907 were able to abolish the aggression, suggesting that the aggressive behavior may be mediated by 5-HT2A receptor. In contrast, MAO B KO mice are resistant to MPTP, a toxin which induces Parkinson's syndromes. Studies of these mice suggest that MAO A and B have distinct biochemical and physiological functions.