A spontaneous point mutation produces monoamine oxidase A/B knock-out mice with greatly elevated monoamines and anxiety-like behavior
A spontaneous point mutation produces monoamine oxidase A/B knock-out mice with greatly elevated monoamines and anxiety-like behavior
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DOI：
10.1074/jbc.m405550200
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发表时间：
2004-09-17
影响因子：
4.8
通讯作者：
Shih, JC
中科院分区：
文献类型：
--
作者：
Chen, K;Holschneider, DP;Shih, JC
第8外显子的自发单胺氧化酶A(MAO A)突变(A863T)引入提前终止密码子，在MAO B KO小鼠群体中产生MAO A/B双基因敲除(KO)小鼠。该突变导致无义介导的mRNA衰变，导致MAO A转录本、蛋白质和催化活性的缺失，并取消了DRAI酶切位点。与野生型小鼠相比，MAO A/B KO小鼠体重减轻。大脑中5-羟色胺、去甲肾上腺素、多巴胺和苯乙胺水平升高，5-羟色胺代谢物5-羟基吲哚乙酸水平下降，降幅远远大于MAO A或B单一KO小鼠。在MAO A/B KO小鼠中观察到的追逐/逃逸和焦虑样行为，不同于MAO A或B单独的KO小鼠，表明不同的单胺水平导致了独特的生化和行为表型。这些小鼠将是研究与异常单胺类神经递质相关的疾病的分子基础的有用模型。
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.