Phenotypic characterization of a new Grin1 mutant mouse generated by ENU mutagenesis

Eur J Neurosci. 2010 Apr;31(7):1281-91. doi: 10.1111/j.1460-9568.2010.07164.x. Epub 2010 Mar 19.


In the RIKEN large-scale N-ethyl-N-nitrosourea (ENU) mutagenesis project we screened mice with a dominant mutation that exhibited abnormal behavior in the open-field test, passive avoidance test and home-cage activity test. We tested 2045 progeny of C57BL/6J males treated with ENU and untreated DBA/2J females in the open-field test and isolated behavioral mutant M100174, which exhibited a significant increase in spontaneous locomotor activity. We identified a missense mutation in the Grin1 gene, which encodes NMDA receptor subunit 1, and designated the mutant gene Grin1(Rgsc174). This mutation results in an arginine to cysteine substitution in the C0 domain of the protein. Detailed analyses revealed that Grin1(Rgsc174) heterozygote exhibited increased novelty-seeking behavior and slight social isolation in comparison with the wild type. In contrast to other Grin1 mutant mice, this mutant exhibited no evidence of heightened anxiety. These results indicate that this is a unique behavioral Grin1 gene mutant mouse that differs from the known Grin1 mutant mice. The results of immunohistochemical and biochemical analyses suggested that impaired interaction between the glutamatergic pathway and dopaminergic pathway may underlie the behavioral phenotypes of the Grin1(Rgsc174) mutant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylating Agents / pharmacology*
  • Amino Acid Sequence
  • Analysis of Variance
  • Animals
  • Arginine / genetics
  • Calcium / metabolism
  • Carrier Proteins / genetics*
  • Cells, Cultured
  • Central Nervous System Stimulants / pharmacology
  • Cerebral Cortex / cytology
  • Chromosome Mapping / methods
  • Cysteine / genetics
  • Embryo, Mammalian
  • Ethylnitrosourea / pharmacology*
  • Exploratory Behavior / drug effects
  • Gene Expression Regulation / drug effects
  • Male
  • Methylphenidate / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Transgenic
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Motor Activity / drug effects
  • Mutagenesis / drug effects*
  • Mutation, Missense
  • N-Methylaspartate / pharmacology
  • Nerve Tissue Proteins / genetics*
  • Neurons
  • Phenazines / pharmacology
  • Phenotype*
  • Proto-Oncogene Proteins c-fos / metabolism
  • Receptors, N-Methyl-D-Aspartate / metabolism


  • Alkylating Agents
  • Carrier Proteins
  • Central Nervous System Stimulants
  • Gprin1 protein, mouse
  • Nerve Tissue Proteins
  • Phenazines
  • Proto-Oncogene Proteins c-fos
  • Receptors, N-Methyl-D-Aspartate
  • 5,10-dihydro-5-methylphenazine
  • Methylphenidate
  • N-Methylaspartate
  • Arginine
  • Mitogen-Activated Protein Kinase 1
  • Cysteine
  • Ethylnitrosourea
  • Calcium