ENU-mutagenesis mice with a non-synonymous mutation in Grin1 exhibit abnormal anxiety-like behaviors, impaired fear memory, and decreased acoustic startle response

BMC Research Notes

Tsuyoshi Miyakawa²  Shigeharu Wakana¹  Tamio Furuse¹  Satoko Hattori³  Hisatsugu Koshimizu³  Keizo Takao²  Juzoh Umemori³ 

[1] Technology and Development Team for Mouse Phenotype Analysis, Japan Mouse Clinic, RIKEN BioResource Center, Tsukuba, Japan;Genetic Engineering and Functional Genomics Group, Frontier Technology Center, Kyoto University Graduate School of Medicine, Kyoto, Japan;Japan Science and Technology Agency (JST), Core Research for Evolutional Science and Technology (CREST), Kawaguchi, Japan

关键词: Schizophrenia;    ADHD;    Psychiatric disorder;    Comprehensive behavioral test battery;    ENU-mutagenesis;    Grin1;    NMDA receptor;   

Others  :  1142642
DOI  :  10.1186/1756-0500-6-203

 received in 2012-11-13, accepted in 2013-05-08,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Umemori et al.; licensee BioMed Central Ltd.

【 图 表 】

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