Ataxia and epileptic seizures in mice lacking type 1 inositol 1,4,5-trisphosphate receptor
Abstract
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.
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The authors identified four dURVs in schizophrenia cases and none in controls in KDM5C, 11 in cases and 2 in controls in KDM5B, and 11 in cases and 3 in controls in ITPR1.
“we identified four dURVs in schizophrenia cases (and none in controls) in XLID gene KDM5C, an H3K4 methylation eraser gene44, 11 dURVs in cases (and 2 in controls) in DD gene KDM5B, another H3K4 methylation eraser gene45, and 11 dURVs in cases (and 3 in controls) in DD gene ITPR1, which encodes an inositol triphosphate receptor46 (Supplementary Tables 2 and 3).”
From Increased burden of ultra-rare protein-altering variants among 4,877 individuals with schizophrenia (2016) · cites this paper as [46]
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- Authors
- Matsumoto, M., Nakagawa, T., Inoue, T., Nagata, E., Tanaka, K., Takano, H., Kuno, J., Sakakibara, S., Yamada, M., Yoneshima, H., Miyawaki, A., Furuichi, Y., Okano, H., Mikoshiba, S. K., & Noda, T.
- Affiliations
- Japanese Foundation For Cancer Research (JP)
- Institute of Medical Science, The University of Tokyo (JP)
- Keio University (JP)
- University of Tsukuba (JP)
- RIKEN (JP)
- ORCID
- Venue
- Nature
- Published
- 1996-01
- Volume
- 379
- Issue
- 6561
- Pages
- 168-171
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2066261176
- Cited by
- 485
- References
- 27
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 6 · 2023: 8 · 2022: 8 · 2021: 12 · 2020: 16 · 2019: 8 · 2018: 14 · 2017: 15 · 2016: 18 · 2015: 10 · 2014: 18 · 2013: 17 · 2012: 21
- FWCI
- 15.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- IP3 receptor, IP3R1, ataxia, epileptic seizures, Purkinje cells, neuronal calcium signaling, developmental lethality, tonic-clonic seizures
- MeSH terms
- Animals, Ataxia, Base Sequence, Brain, Cell Line, Electroencephalography, Epilepsy, Fetal Death, Molecular Sequence Data, Mutation, Purkinje Cells, Calcium Channels, Inositol 1,4,5-Trisphosphate, DNA Primers, Receptors, Cytoplasmic and Nuclear, Gene Targeting, Mice, Inositol 1,4,5-Trisphosphate Receptors
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