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 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.
Department of Molecular Pharmacology and Toxicology, University of Southern California School of Pharmacy, Los Angeles, California 90089-9121, USA.
Kevin
K
Chen
Daniel P
DP
Holschneider
Weihua
W
Wu
Igor
I
Rebrin
Jean C
JC
Shih
D000595:Amino Acid Sequence; D000818:Animals; D001007:Anxiety / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D001483:Base Sequence; D001522:Behavior, Animal / Q000502:physiology; D015306:Biogenic Monoamines / Q000378:metabolism*; D018389:Codon, Nonsense; D005091:Exons; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D008995:Monoamine Oxidase / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D017354:Point Mutation; D012333:RNA, Messenger / Q000378:metabolism
D015306:Biogenic Monoamines; D018389:Codon, Nonsense; D012333:RNA, Messenger; D008995:Monoamine Oxidase