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 InsP(3) receptor (IP(3)R1) is the major neuronal member of the IP(3)R family in the central nervous system(3,4), predominantly enriched in cerebellar Purkinje cells but also concentrated in neurons in the hippocampal CA1 region, caudate-putamen, and cerebral cortex(5,6). Here we report that most IP(3)R1-deficient mice generated by gene targeting die in utero, and born animals have severe ataxia and tonic or tonic-clonic seizures and die by the weaning period. An electroencephalogram showed that they suffer from epilepsy, indicating that IP(3)R1 is essential 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 electrophysiological properties of the cerebellar Purkinje cells of IP(3)R1-deficient mice were not severely impaired.