title: Rescue of abnormal phenotypes of the delta2 glutamate receptor-null mice by mutant delta2 transgenes.
abstract: The delta2 glutamate receptor (GluRdelta2) has a crucial role in cerebellar functions; disruption of GluRdelta2 alleles in mice (delta2(-/-)) 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 GluRdelta2 is activated by glutamate analogues. Here we introduced a GluRdelta2 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 delta2(-/-) mice. Surprisingly, a mutant GluRdelta2 transgene, as well as a wild-type GluRdelta2 transgene, rescued all abnormal phenotypes of delta2(-/-) 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 GluRdelta2 functions in delta2(-/-) mice.
authors.affiliation: Deptartment of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Hirai
authors.forename: Taisuke
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Wataru
authors.initials: W
authors.lastname: Kakegawa
authors.forename: Shinji
authors.initials: S
authors.lastname: Matsuda
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Mishina
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Michisuke
authors.initials: M
authors.lastname: Yuzaki
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000235:genetics / Q000378:metabolism; D001522:Behavior, Animal; D004594:Electrophysiology; D015870:Gene Expression; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D018408:Patch-Clamp Techniques; D010641:Phenotype; D017470:Receptors, Glutamate / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D016415:Sequence Alignment; D013569:Synapses / Q000378:metabolism; D019076:Transgenes / Q000235:genetics*
chemical_list: D017470:Receptors, Glutamate; C107913:glutamate receptor delta 2; D001120:Arginine