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首页> 外文期刊>BMC research notes >ENU-mutagenesis mice with a non-synonymous mutation in Grin1 exhibit abnormal anxiety-like behaviors, impaired fear memory, and decreased acoustic startle response
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ENU-mutagenesis mice with a non-synonymous mutation in Grin1 exhibit abnormal anxiety-like behaviors, impaired fear memory, and decreased acoustic startle response

机译：在Grin1中具有非同义突变的ENU突变小鼠表现出异常的焦虑样行为，恐惧记忆受损和听觉惊吓反应降低

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Background The Grin1 (glutamate receptor, ionotropic, NMDA1) gene expresses a subunit of N-methyl-D-aspartate ( NMDA ) receptors that is considered to play an important role in excitatory neurotransmission, synaptic plasticity, and brain development. Grin1 is a candidate susceptibility gene for neuropsychiatric disorders, including schizophrenia, bipolar disorder, and attention deficit/hyperactivity disorder ( ADHD ). In our previous study, we examined an N -ethyl- N -nitrosourea (ENU)-generated mutant mouse strain ( Grin1 Rgsc174/ Grin1 +) that has a non-synonymous mutation in Grin1 . These mutant mice showed hyperactivity, increased novelty-seeking to objects, and abnormal social interactions. Therefore, Grin1 Rgsc174/ Grin1 + mice may serve as a potential animal model of neuropsychiatric disorders. However, other behavioral characteristics related to these disorders, such as working memory function and sensorimotor gating, have not been fully explored in these mutant mice. In this study, to further investigate the behavioral phenotypes of Grin1 Rgsc174/ Grin1 + mice, we subjected them to a comprehensive battery of behavioral tests. Results There was no significant difference in nociception between Grin1 Rgsc174/ Grin1 + and wild-type mice. The mutants did not display any abnormalities in the Porsolt forced swim and tail suspension tests. We confirmed the previous observations that the locomotor activity of these mutant mice increased in the open field and home cage activity tests. They displayed abnormal anxiety-like behaviors in the light/dark transition and the elevated plus maze tests. Both contextual and cued fear memory were severely deficient in the fear conditioning test. The mutant mice exhibited slightly impaired working memory in the eight-arm radial maze test. The startle amplitude was markedly decreased in Grin1 Rgsc174/ Grin1 + mice, whereas no significant differences between genotypes were detected in the prepulse inhibition (PPI) test. The mutant mice showed no obvious deficits in social behaviors in three different social interaction tests. Conclusions This study demonstrated that the Grin1 Rgsc174/ Grin1 + mutation causes abnormal anxiety-like behaviors, a deficiency in fear memory, and a decreased startle amplitude in mice. Although Grin1 Rgsc174/ Grin1 + mice only partially recapitulate symptoms of patients with ADHD , schizophrenia, and bipolar disorder, they may serve as a unique animal model of a certain subpopulation of patients with these disorders.
机译：背景Grin1（谷氨酸受体，离子型，NMDA1）基因表达N-甲基-D-天冬氨酸（NMDA）受体的亚基，被认为在兴奋性神经传递，突触可塑性和大脑发育中起重要作用。 Grin1是神经精神疾病（包括精神分裂症，双相情感障碍和注意缺陷/多动障碍（ADHD））的候选易感基因。在我们以前的研究中，我们检查了由N-乙基-N-亚硝基脲（ENU）产生的突变小鼠品系（Grin1 Rgsc174 / Grin1 + ）在Grin1中具有非同义突变。这些突变小鼠表现出活动过度，对物体的新颖性增加以及异常的社交互动。因此，Grin1 Rgsc174 / Grin1 + 小鼠可能是潜在的神经精神疾病动物模型。但是，与这些疾病有关的其他行为特征，例如工作记忆功能和感觉运动门控，尚未在这些突变小鼠中得到充分探索。在这项研究中，为进一步研究Grin1 Rgsc174 / Grin1 + 小鼠的行为表型，我们对他们进行了全面的行为测试。结果Grin1 Rgsc174 / Grin1 + 与野生型之间的伤害感受没有显着差异老鼠。突变体在Porsolt强迫游泳和尾巴悬吊测试中未显示任何异常。我们证实了以前的观察结果，这些突变小鼠的运动活动在开放领域和家庭笼活动测试中增加。他们在明暗过渡和高架迷宫测试中表现出异常的焦虑样行为。在恐惧条件测试中，上下文和暗示的恐惧记忆都严重不足。在八臂径向迷宫测试中，突变小鼠表现出略微受损的工作记忆。 Grin1 Rgsc174 / Grin1 + 小鼠的惊吓幅度明显降低，但无显着差异在脉冲前抑制（PPI）测试中检测到基因型之间的差异。在三种不同的社交互动测试中，突变小鼠均未表现出明显的社交行为缺陷。结论这项研究表明，Grin1 Rgsc174 / Grin1 + 突变会引起异常的焦虑样行为。 ，恐惧记忆不足和小鼠惊吓幅度降低。尽管Grin1 Rgsc174 / Grin1 + 小鼠仅部分概括了ADHD，精神分裂症，和双相情感障碍，它们可以作为这些疾病患者某些亚群的独特动物模型。

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