MAO-A and -B gene knock-out mice exhibit distinctly different behavior.
MAO-A and -B are key isoenzymes that degrade biogenic and dietary amines. MAO-A preferentially oxidizes 5-HT and NE, whereas MAO-B preferentially oxidizes PEA. However, the substrate and inhibitor selectivity overlap depending on the concentration of the enzyme and substrate. A line of transgenic mice has been generated in which the gene that encodes MAO-A is disrupted. MAO-A 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. We have also generated mice deficient in MAO-B by homologous recombination. Interestingly, MAO-B KO mice do not exhibit aggression and only levels of PEA are increased. MAO-B-deficient mice are resistant to the Parkinsongenic neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Thus, studies of MAO-A and -B KO mice have clearly shown that MAO-A and -B have distinct functions in neurotransmitter metabolism and behavior. MAO KO mice are valuable models for investigating the role of monoamines in aggression and neurodegenerative and stress-related disorders.
Shih
J C
JC
Department of Molecular Pharmacology and Toxicology, University of Southern California, School of Pharmacy, Los Angeles 90033, USA.
Chen
K
K
D000374:Aggression / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008995:Monoamine Oxidase / Q000235:genetics / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000627:therapeutic use; D009638:Norepinephrine / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D013312:Stress, Physiological / Q000188:drug therapy / Q000378:metabolism*
D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D012701:Serotonin; D008995:Monoamine Oxidase; D009638:Norepinephrine