Jun 2010 A model for psychiatric disorder


A model for psychiatric disorder

M100174 RBRC GSC 0036
Mutated gene:Grin1, Chr 2
Allele symbol:Grin1Rgsc174

Wild type


The heterozygote was hyperactive and exhibited inattention to another mouse.
The frequency of interaction with another subject of the same genotype as the heterozygote was initially similar to that of the wild type (left), but thereafter the heterozygote spent a shorter time interacting with the other subject (right).
 Effect of MPH on the locomotor activity of +/+ mice and Grin1Rgsc174/+
The distance traveled by wild-type (left) andGrin1Rgsc174/+ (right) mice in the open field for 20 min following saline or MPH injection. Error bars represent SEM of male mice (n = 10; 11 weeks old) of each genotype.


   The founder mouse, M100174, exhibited a significant increase in spontaneous locomotor activity in an open-field test. A C to T missense mutation was identified in exon 18 of the Grin1 gene and resulted in an arginine to cysteine substitution in the C0 domain of the protein. Detailed analyses revealed that the Grin1Rgsc174 heterozygote exhibited increased novelty-seeking behavior and slight social isolation compared with the wild type. Additionally, the hyperlocomotor activity of the heterozygote was decreased by methylphenidate (MPH) administration. MPH is one of the main therapeutic agents used to treat attention-deficit hyperactivity disorder (ADHD) and narcolepsy. Phenotypes ofGrin1Rgsc174 indicate that this mutant displays some of the signs and symptoms of psychiatric disorders including ADHD.


Depositor : Mouse Functional Genomics Research Group, RIKEN Genomic Sciences Center
Reference : Furuse T et al. Phenotypic characterization of a new Grin1 mutant mouse generated by ENU mutagenesis. European Journal of Neuroscience 31(7):1281-1291, 2010.

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