Premium
Phenotypic characterization of a new Grin1 mutant mouse generated by ENU mutagenesis
Author(s) -
Furuse Tamio,
Wada Yumiko,
Hattori Kotaro,
Yamada Ikuko,
Kushida Tomoko,
Shibukawa Yoko,
Masuya Hiroshi,
Kaneda Hideki,
Miura Ikuo,
Seno Naoki,
Kanda Tomoyuki,
Hirose Ryo,
Toki Shinichiro,
Nakanishi Kousuke,
Kobayashi Kimio,
Sezutsu Hideki,
Gondo Yoichi,
Noda Tetsuo,
Yuasa Shigeki,
Wakana Shigeharu
Publication year - 2010
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2010.07164.x
Subject(s) - mutant , mutagenesis , biology , mutation , phenotype , open field , genetics , microbiology and biotechnology , gene , endocrinology
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.