RRC ID 11805
Author Furuse T, Wada Y, Hattori K, Yamada I, Kushida T, Shibukawa Y, Masuya H, Kaneda H, Miura I, Seno N, Kanda T, Hirose R, Toki S, Nakanishi K, Kobayashi K, Sezutsu H, Gondo Y, Noda T, Yuasa S, Wakana S.
Title Phenotypic characterization of a new Grin1 mutant mouse generated by ENU mutagenesis.
Journal Eur. J. Neurosci.
Abstract 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.
Volume 31(7)
Pages 1281-91
Published 2010-4
DOI 10.1111/j.1460-9568.2010.07164.x
PMID 20345915
MeSH 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
IF 2.832
Times Cited 12
Mice M100174