A Spontaneous Point Mutation Produces Monoamine Oxidase A/B Knock-out Mice with Greatly Elevated Monoamines and Anxiety-like Behavior

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 cata...

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Bibliographic Details
Published in:The Journal of biological chemistry 2004-09, Vol.279 (38), p.39645-39652
Main Authors: Chen, Kevin, Holschneider, Daniel P., Wu, Weihua, Rebrin, Igor, Shih, Jean C.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Anxiety - genetics
Anxiety - metabolism
Anxiety - physiopathology
Base Sequence
Behavior, Animal - physiology
Biogenic Monoamines - metabolism
Codon, Nonsense
Exons
Female
Male
Mice
Mice, Knockout
Molecular Sequence Data
Monoamine Oxidase - genetics
Monoamine Oxidase - metabolism
Phenotype
Point Mutation
RNA, Messenger - metabolism
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Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M405550200