Matsumoto M, Nakagawa T, Inoue T, Nagata E, Tanaka K, Takano H, Minowa O, Kuno J, Sakakibara S, Yamada M, Yoneshima H, Miyawaki A, Fukuuchi Y, Furuichi T, Okano H, Mikoshiba K, Noda T
Department of Molecular Neurobiology, University of Tokyo, Japan.
Nature. 1996 Jan 11;379(6561):168-71. doi: 10.1038/379168a0.
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.
肌醇1,4,5-三磷酸（InsP3）受体在多种细胞类型中作为InsP3门控的Ca2+释放通道发挥作用。1型InsP3受体（IP3R1）是中枢神经系统中IP3R家族的主要神经元成员，主要富集于小脑浦肯野细胞，但也集中于海马CA1区、尾状核-壳核和大脑皮层的神经元中。在此我们报告，通过基因靶向产生的大多数IP3R1缺陷小鼠在子宫内死亡，出生的动物有严重共济失调和强直性或强直性阵挛性癫痫发作，并在断奶期死亡。脑电图显示它们患有癫痫，表明IP3R1对正常脑功能至关重要。然而，对IP3R1缺陷小鼠的脑和外周组织进行苏木精-伊红染色后的光学显微镜观察未发现异常，并且IP3R1缺陷小鼠小脑浦肯野细胞的独特电生理特性也未受到严重损害。
