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Increased stress response and β–phenylethylamine in MAOB–deficient mice

Nature Genetics volume 17, pages 206–210 (1997)Cite this article

Abstract

MAOA and MAOB are key iso-enzymes that degrade biogenic and dietary amines1–5. MAOA preferentially oxidizes serotonin (5-hydroxytryptamine, or 5-HT) and nore-pinephrine (NE), whereas MAOB preferentially oxidizes β-phenylethylamine (PEA). Both forms can oxidize dopamine (DA). A mutation in MAOA results in a clinical phenotype characterized by borderline mental retardation and impaired impulse control6,7. X-chromosomal deletions which include MAOB were found in patients suffering from atypical Norrie's disease8,9, which is characterized by blindness and impaired hearing. Reduced MAOB activity has been found in type-ll alcoholism and in cigarette smokers10,11. Because most alcoholics smoke, the effects of alcohol on MAOB activity remain to be determined. Here we show that targetted inactivation of MAOB in mice increases levels of PEA but not those of 5-HT, NE and DA, demonstrating a primary role for MAOB in the metabolism of PEA. PEA has been implicated in modulating mood and affect12,13. Indeed, MAOB-deficient mice showed an increased reactivity to stress. In addition, mutant mice were resistant to the neurodegenerative effects of MPTP, a toxin that induces a condition reminiscent of Parkinson's disease.

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Authors and Affiliations

  1. Department of Molecular Pharmacology and Toxicology, School of Pharmacy, and University of Southern California, Los Angeles, California, 90033, USA

    Joseph Grimsby, Kevin Chen, Takeshi Kumazawa, Lori Klaidman, James D. Adams & Jean C. Shih

  2. Department of Cell and Neurobiology, School of Medicine, University of Southern California, Los Angeles, California, 90033, USA

    Jean C. Shih

  3. Department of Pharmacology, Cornell University Medical College, New York, New York, 10021, USA

    Miklos Toth & Judit Gal

  4. Department of Psychology and Pharmacology, NIMH, St. Elizabeth's Hospital, Washington, DC, 20032, USA

    Farouk Karoum

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Correspondence to Jean C. Shih.

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Grimsby, J., Toth, M., Chen, K. et al. Increased stress response and β–phenylethylamine in MAOB–deficient mice. Nat Genet 17, 206–210 (1997). https://doi.org/10.1038/ng1097-206

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