title: Type 1 inositol 1,4,5-trisphosphate receptor knock-out mice: their phenotypes and their meaning in neuroscience and clinical practice.
abstract: Cytoplasmic calcium, which acts as a second messenger, is derived not only from outside the cell but also from intracellular stores. A receptor for inositol 1,4,5-trisphosphate (IP3), an intracellular second messenger, is located on these internal calcium stores and functions as a calcium releasing channel. The "type 1" IP3 receptor (IP3R1) is concentrated predominantly in cerebellar Purkinje cells and is also widely present in other neural and peripheral tissues, but many of its physiological roles in these cells are still unclear. We have previously succeeded in obtaining mice with disruption of this IP3R1 gene, in which brain IP3-induced calcium release was almost completely abolished. They were rarely born alive, indicating that IP3R1 has some functions during embryonic development. Animals exhibited severe neurological symptoms, ataxia and epilepsy, and were shown to be deficient in the cerebellar long-term depression. They give us promising clues regarding the physiological roles of calcium release from internal stores and serve as a model for the relevant human disease states.
authors.affiliation: Brain Science Institute, Institute of Physical and Chemical Research (RIKEN), and Department of Molecular Neurobiology, University of Tokyo, Japan. matsumot@ims.u-tokyo.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Matsumoto
authors.forename: E
authors.initials: E
authors.lastname: Nagata
mesh_terms: D000818:Animals; D001259:Ataxia / Q000503:physiopathology*; D001921:Brain / Q000378:metabolism / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000502:physiology*; D004594:Electrophysiology; D004827:Epilepsy / Q000503:physiopathology*; D015544:Inositol 1,4,5-Trisphosphate / Q000235:genetics / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000502:physiology*
chemical_list: D015220:Calcium Channels; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium