ATAXIA AND EPILEPTIC SEIZURES IN MICE LACKING TYPE-1 INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR

THE inositol 1,4,5-trisphosphate (InsP(3)) receptor acts as an InsP(3) -gated Ca2+ release channel in a variety of cell types(1,2). Type 1 In sP(3) receptor (IP(3)R1) is the major neuronal member of the IP(3)R fa mily in the central nervous system(3,4), predominantly enriched in cer ebellar Purkinje cells but also concentrated in neurons in the hippoca mpal CA1 region, caudate-putamen, and cerebral cortex(5,6). Here we re port that most IP(3)R1-deficient mice generated by gene targeting die in utero, and born animals have severe ataxia and tonic or tonic-cloni c seizures and die by the weaning period. An electroencephalogram show ed that they suffer from epilepsy, indicating that IP(3)R1 is essentia l for proper brain function. However, observation by light microscope of the haematoxylin-eosin staining of the brain and peripheral tissues of IP(3)R1-deficient mice showed no abnormality, and the unique elect rophysiological properties of the cerebellar Purkinje cells of IP(3)R1 -deficient mice were not severely impaired.