Rescue of abnormal phenotypes of the δ2 glutamate receptor-null mice by mutant δ2 transgenes

Hirdkazu Hirai, Taisuke Miyazaki, Wataru Kakegawa, Shinji Matsuda, Masayoshi Mishina, Masahiko Watanabe, Michisuke Yuzaki

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

The δ2 glutamate receptor (GluR52) has a crucial role in cerebellar functions; disruption of GluRδ2 alleles in mice (δ2-/-) impairs synapse formation and long-term depression, which is thought to underlie motor learning in the cerebellum, and consequently leads to motor discoordination. However, it has been unclear whether GluRδ2 is activated by glutamate analogues. Here we introduced a GluRδ2 transgene, which had a mutation (Arg514Lys) in the putative ligand-binding motif conserved in all mammalian ionotropic glutamate receptors (iGluRs) and their ancestral bacterial periplasmic amino-acid-binding proteins, into δ2-/- mice. Surprisingly, a mutant GluRδ2 transgene, as well as a wild-type GluRδ2 transgene, rescued all abnormal phenotypes of δ2 -/- mice. Therefore, these results indicate that the conserved arginine residue, which is crucial for the binding of iGluRs to glutamate analogues, is not essential for the restoration of GluRδ2 functions in δ2-/- mice.

Original languageEnglish
Pages (from-to)90-95
Number of pages6
JournalEMBO Reports
Volume6
Issue number1
DOIs
Publication statusPublished - 2005

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Ionotropic Glutamate Receptors
Glutamate Receptors
Transgenes
Glutamic Acid
Phenotype
Restoration
Arginine
Carrier Proteins
Ligands
Amino Acids
Synapses
Cerebellum
Alleles
Learning
Depression
Mutation

Keywords

  • Cerebellum
  • Glutamate receptor
  • LTD
  • Mouse
  • Purkinje cell

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Rescue of abnormal phenotypes of the δ2 glutamate receptor-null mice by mutant δ2 transgenes. / Hirai, Hirdkazu; Miyazaki, Taisuke; Kakegawa, Wataru; Matsuda, Shinji; Mishina, Masayoshi; Watanabe, Masahiko; Yuzaki, Michisuke.

In: EMBO Reports, Vol. 6, No. 1, 2005, p. 90-95.

Research output: Contribution to journalArticle

Hirai, Hirdkazu ; Miyazaki, Taisuke ; Kakegawa, Wataru ; Matsuda, Shinji ; Mishina, Masayoshi ; Watanabe, Masahiko ; Yuzaki, Michisuke. / Rescue of abnormal phenotypes of the δ2 glutamate receptor-null mice by mutant δ2 transgenes. In: EMBO Reports. 2005 ; Vol. 6, No. 1. pp. 90-95.
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