Rescue of abnormal phenotypes of the delta2 glutamate receptor-null mice by mutant delta2 transgenes.
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.
Hirai
Hirokazu
H
Deptartment of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Miyazaki
Taisuke
T
Kakegawa
Wataru
W
Matsuda
Shinji
S
Mishina
Masayoshi
M
Watanabe
Masahiko
M
Yuzaki
Michisuke
M
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*
D017470:Receptors, Glutamate; C107913:glutamate receptor delta 2; D001120:Arginine