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.
Shih
Jean Chen
JC
Department of Molecular Pharmacology and Toxicology, Pharmaceutical Science Center, University of Southern California, 1985 Zonal Ave, Los Angeles, CA 90033, USA. jcshih@usc.edu
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular / Q000379:methods*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D008995:Monoamine Oxidase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
D008995:Monoamine Oxidase