Monoamine oxidase: From genes to behavior

Cloning of MAO (monoamine oxidase) A and B has demonstrated unequivocally t hat these enzymes are made up of different polypeptides, and our understand ing of MAO structure, regulation, and function has been significantly advan ced by studies using their cDNA. MAO A and B genes are located on the X-chr omosome (Xp 11.23) and comprise 15 exons with identical intron-exon organiz ation, which suggests that they are derived from the same ancestral gene. M AO A and B knockout mice exhibit distinct differences in neurotransmitter m etabolism and behavior. MAO A knock-out mice have elevated brain levels of serotonin, norephinephrine, and dopamine and manifest aggressive behavior s imilar to human males with a deletion of MAO A. In contrast, MAO B knock-ou t mice do nor exhibit aggression and only levels of phenylethylamine are in creased. Mite lacking MAO B are resistant to the Parkinsongenic neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Both MAO A and B knock-out m ice show increased reactivity to stress. These knock-out mice are valuable models for investigating the role of monoamines in psychoses and neurodegen erative and stress-related disorders.