Behavioral and regulatory abnormalities in mice deficient in the NPAS1 and NPAS3 transcription factors
Behavioral and regulatory abnormalities in mice deficient in the NPAS1 and NPAS3 transcription factors
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DOI：
10.1073/pnas.0405310101
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发表时间：
2004-09-14
影响因子：
11.1
通讯作者：
McKnight, SL
中科院分区：
文献类型：
--
作者：
Erbel-Sieler, C;Dudley, C;McKnight, SL
在编码NPAS 1和NPAS 3转录因子的基因中携带失活突变的实验室小鼠已显示出一系列行为和神经化学异常。行为异常包括惊吓反应减弱（通过前脉冲抑制测量）和社会认知受损。NPAS 1/NPAS 3缺陷小鼠在断奶时也表现出刻板的飞镖行为和增加的运动活性。免疫组织化学染色分析表明，NPAS 1和NPAS 3蛋白表达在抑制性中间神经元和这些神经元的活力和解剖分布不受任何转录因子的情况下。来自NPAS 3-和NPAS 1/NPAS 3-缺陷小鼠的成年脑组织表现出reelin的明显减少，reelin是一种大的分泌蛋白，据报道其表达在精神分裂症患者的死后脑组织中减弱。这些观察结果提出了这样的可能性：抑制性中间神经元中由NPAS 1和NPAS 3转录因子控制的调节程序可能与精神病有实质性或间接相关。
Laboratory mice bearing inactivating mutations in the genes encoding the NPAS1 and NPAS3 transcription factors have been shown to exhibit a spectrum of behavioral and neurochemical abnormalities. Behavioral abnormalities included diminished startle response, as measured by prepulse inhibition, and impaired social recognition. NPAS1/NPAS3-deficient mice also exhibited stereotypic darting behavior at weaning and increased locomotor activity. Immunohistochemical staining assays showed that the NPAS1 and NPAS3 proteins are expressed in inhibitory interneurons and that the viability and anatomical distribution of these neurons are unaffected by the absence of either transcription factor. Adult brain tissues from NPAS3- and NPAS1/NPAS3-deficient mice exhibited a distinct reduction in reelin, a large, secreted protein whose expression has been reported to be attenuated in the postmortem brain tissue of patients with schizophrenia. These observations raise the possibility that a regulatory program controlled in inhibitory interneurons by the NPAS1 and NPAS3 transcription factors may be either substantively or tangentially relevant to psychosis.