A spontaneous point mutation produces monoamine oxidase A/B knock-out mice with greatly elevated monoamines and anxiety-like behavior.

Abstract

A spontaneous monoamine oxidase A (MAO A) mutation (A863T) in exon 8 introduced a premature stop codon, which produced MAO A/B double knock-out (KO) mice in a MAO B KO mouse colony. This mutation caused a nonsense-mediated mRNA decay and resulted in the absence of MAO A transcript, protein, and catalytic activity and abrogates a DraI restriction site. The MAO A/B KO mice showed reduced body weight compared with wild type mice. Brain levels of serotonin, norepinephrine, dopamine, and phenylethylamine increased, and serotonin metabolite 5-hydroxyindoleacetic acid levels decreased, to a much greater degree than in either MAO A or B single KO mice. Observed chase/escape and anxiety-like behavior in the MAO A/B KO mice, different from MAO A or B single KO mice, suggest that varying monoamine levels result in both a unique biochemical and behavioral phenotype. These mice will be useful models for studying the molecular basis of disorders associated with abnormal monoamine neurotransmitters.

• Authors: Kevin Chen, Daniel P Holschneider, Weihua Wu, Igor Rebrin, Jean C Shih
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 279 Issue 38 Pg. 39645-52 (Sep 17 2004) ISSN: 0021-9258 [Print] United States
• PMID: 15272015 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Biogenic Monoamines
• Codon, Nonsense
• RNA, Messenger
• Monoamine Oxidase

Topics

• Amino Acid Sequence
• Animals
• Anxiety (genetics, metabolism, physiopathology)
• Base Sequence
• Behavior, Animal (physiology)
• Biogenic Monoamines (metabolism)
• Codon, Nonsense
• Exons
• Female
• Male
• Mice
• Mice, Knockout
• Molecular Sequence Data
• Monoamine Oxidase (genetics, metabolism)
• Phenotype
• Point Mutation
• RNA, Messenger (metabolism)