ABSTRACT
Monoamine oxidase A and B (MAO-A and MAO-B) are important isoenzymes which catalyze the oxidation deamination of biogenic and dietary amines in the brain and in the periphery with the production of hydrogen peroxide (H20 2) (1,2). MAO-A has higher affinity for the substrates serotonin (5-HT), norepinephrine (NE), dopamine (DA), and the inhibitor clorgyline whereas MAO-B has higher affinity for phenylethylamine (PEA), benzylamine, and the inhibitor deprenyl (3). These isoenzymes are made of different polypeptides (4,5) located on the X chromosome (6,7) and have identical intron and exon organization (8). Different cysteines are important for the catalytic activity of MAO-A and B (9), and distinct domains confer their substrate specificity (10). The different cis and trans ele ments in the promotor suggest that the regulation of these two genes is different (11,12). A line of transgenic mice has been generated in which the gene that encodes MAO-A is disrupted. MAO-A knock-out (KO) mice have elevated brain levels of 5-HT, NE, and DA and manifest aggressive behavior similar to men with a deletion of MAO-A (4,13,14). Emotional learning and memory are also increased in MAO-A KO mice (15). We have also generated mice deficient in MAO-B by homologous recombination. MAO-B KO mice do not exhibit aggres sion and only levels of PEA are increased. Mice lacking MAO-B are also resistant to the Parkinsongenic neurotoxin l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) (16). Both MAO-A (17) and MAO-B KO (16) mice show increased reactivity to stress. Thus, studies of MAO-A and MAO-B KO mice have clearly shown that MAO-A and B have distinct functions in neurotransmitter metabolism and behavior. These KO mice are valuable models for investigating the role of monoamines in psychoses, neurodegenerative, and stress-related disorders. In this
chapter we will discuss the behavior and monoamine metabolism of mice defi cient in MAO-A and B and future research directions using KO mice.
