PMID:11985881

Citation	Ueno, T, Kameyama, K, Hirata, M, Ogawa, M, Hatsuse, H, Takagaki, Y, Ohmura, M, Osawa, N and Kudo, Y (2002) A mouse with a point mutation in plasma membrane Ca2+-ATPase isoform 2 gene showed the reduced Ca2+ influx in cerebellar neurons. Neurosci. Res. 42:287-97
Abstract	We analyzed mutant mice showing behavioral defects such as severe tremor, up-and-down and side-to-side wriggling of neck without coordination, and found that the gene causing the defects was located between 46 and 60.55 centimorgans (cM) on the mouse chromosome 6. In this region, nucleotide transition of the plasma membrane Ca2+-ATPase isoform 2 (PMCA2) gene was found, which caused a glutamic acid to change into lysine. Since PMCA2 is expressed in the cerebellum and plays an important role to maintain the homeostasis of the intracellular Ca2+ as a Ca2+ pump, the behavioral defect can be ascribed to the impairment of Ca2+ regulation in neurons of the cerebellum. To confirm the defect of Ca2+ homeostasis in the mutant mice, we measured high K+-induced changes in intracellular Ca2+ concentration ([Ca2+]i) in the cerebellar neurons. Contrary to our expectation, the extent of the [Ca2+]i increase in all the regions tested in the cerebellar slice was far smaller than that of the wild type mice, while the resting [Ca2+]i remained almost unaltered. The rate of rise in [Ca2+]i during high K+-induced depolarization was significantly reduced, and the extrusion rate of increased [Ca2+]i was also reduced. These results suggested that voltage-gated Ca2+ channels were down-regulated in the mutant mice in order to regulate [Ca2+]i toward the normal homeostasis. The behavioral defects may be ascribed to the down-regulated Ca2+ homeostasis since dynamic changes in [Ca2+]i are important for various neuronal functions.
Links	PubMed
Keywords	Animals; Behavior, Animal/physiology; Calcium/metabolism; Calcium Signaling/genetics; Calcium-Transporting ATPases/deficiency; Calcium-Transporting ATPases/genetics; Cation Transport Proteins; Cell Membrane/metabolism; Cerebellum/growth & development; Cerebellum/metabolism; Cerebellum/physiopathology; Chromosomes/genetics; DNA Mutational Analysis; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Female; Genotype; Homeodomain Proteins; Male; Mice; Mice, Mutant Strains; Molecular Sequence Data; Neurons/metabolism; Nucleotides/genetics; Phenotype; Plasma Membrane Calcium-Transporting ATPases; Point Mutation/physiology; Protozoan Proteins; Purkinje Cells/metabolism; Purkinje Cells/pathology; RNA, Messenger/genetics; RNA, Messenger/metabolism; Sequence Homology, Amino Acid; Sequence Homology, Nucleic Acid
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