title: Ho15J: a new hotfoot allele in a hot spot in the gene encoding the delta2 glutamate receptor.
abstract: Hotfoot, a recessive mouse mutation characterized by ataxia and jerky movements of the hindlimbs, is caused by various mutations in the gene (Grid2) encoding the delta2 glutamate receptor (GluRdelta2). So far, at least 20 alleles, arising either spontaneously or through the random insertion of transgenes, have been described. Interestingly, most hotfoot mutants have deletions of one or more exons coding for portions of the most amino-terminal domain of GluRdelta2. However, because live mice colonies are no longer available for most hotfoot mutants, the possibility that the loss of a part of an intron might affect the splicing of other exons or the general efficiency of transcription could not be ruled out. Here, we report that a newly identified hotfoot mutant, ho15J, was caused by an intragenic deletion of the Grid2 gene, which indeed resulted in a new type of 52-amino-acid deletion in the most amino-terminal domain of GluRdelta2. Like GluRdelta2 proteins in ho4J mutants, GluRdelta2 proteins in ho15J mice were retained in the soma of Purkinje cells, where they were degraded. Long-term depression, a form of synaptic plasticity underlying information storage in the cerebellum, was abrogated, and ho15J mice showed severe motor discoordination on rotarod tests. The agreement between the PCR results for genomic DNA and the RT-PCR results for the ho15J allele supports the view that PCR analyses of grid2 genomic DNA can predict alterations in mRNA and protein. In addition, the present findings underscore the importance of the most amino-terminal domain in GluRdelta2 signaling and cerebellar functions.
authors.affiliation: Department of Physiology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Motohashi
authors.forename: Wataru
authors.initials: W
authors.lastname: Kakegawa
authors.forename: Michisuke
authors.initials: M
authors.lastname: Yuzaki
mesh_terms: D000483:Alleles; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002531:Cerebellum / Q000166:cytology; D023281:Genomics / Q000379:methods; D066298:In Vitro Techniques; D018782:Maze Learning / Q000502:physiology; D008564:Membrane Potentials / Q000235:genetics; D051379:Mice; D008818:Mice, Neurologic Mutants / Q000235:genetics / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011597:Psychomotor Performance / Q000502:physiology; D011689:Purkinje Cells / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D017470:Receptors, Glutamate / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D017384:Sequence Deletion
chemical_list: D012333:RNA, Messenger; D017470:Receptors, Glutamate; C107913:glutamate receptor delta 2