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.
Chen
Kevin
K
Department of Molecular Pharmacology and Toxicology, University of Southern California School of Pharmacy, Los Angeles, California 90089-9121, USA.
Holschneider
Daniel P
DP
Wu
Weihua
W
Rebrin
Igor
I
Shih
Jean C
JC
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