Ataxia and epileptic seizures in mice lacking type 1 inositol 1,4,5-trisphosphate receptor

The inositol 1,4,5-trisphosphate (InsP₃) receptor acts as an InsP₃-gated Ca²⁺ release channel in a variety of cell types. Type 1 InsP₃ receptor (IP₃R1) is the major neuronal member of the IP₃R family in the central nervous system, predominantly enriched in cerebellar Purkinje cells but also concentrated in neurons in the hippocampal CA1 region, caudate-putamen, and cerebral cortex. Here we report that most IP₃R1-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 IP₃R1 is essential for proper brain function. However, observation by light microscope of the haematoxylin-eosin staining of the brain and peripheral tissues of IP₃R1-deficient mice showed no abnormality, and the unique electrophysiological properties of the cerebellar Purkinje cells of IP₃R1 deficient mice were not severely impaired.