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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 types1,2. Type 1 InsP3 receptor (IP3R1) is the major neuronal member of the IP3R family in the central nervous system3,4, predominantly enriched in cerebellar Purkinje cells but also concentrated in neurons in the hippocampal CA1 region, caudate-putamen, and cerebral cortex5,6. 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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References

  1. Berridge, M. J. Nature 361, 315–325 (1993).

    Article  ADS  CAS  Google Scholar 

  2. Mikoshiba, K. Trends pharmacol. Sci. 14, 86–89 (1993).

    Article  CAS  Google Scholar 

  3. Yamamoto-Hino, M. et al. NeuroReport 6, 273–276 (1995).

    Article  CAS  Google Scholar 

  4. Furuichi, T., Kohda, K., Miyawaki, A. & Mikoshiba, K. Curr. Opin. Neurobiol. 4, 294–303 (1994).

    Article  CAS  Google Scholar 

  5. Nakanishi, S., Maeda, N. & Mikoshiba, K. J. Neurosci. 11, 2075–2086 (1991).

    Article  CAS  Google Scholar 

  6. Furuichi, T. et al. Receptors and Channels 1, 11–24 (1993).

    CAS  PubMed  Google Scholar 

  7. Takeshima, H. et al. Nature. 369, 556–559 (1994).

    Article  ADS  CAS  Google Scholar 

  8. De Smedt, D. H. et al. J. biol. Chem. 269, 21691–21698 (1994).

    CAS  PubMed  Google Scholar 

  9. Yagisawa, H. et al. J. biol. Chem. 269, 20179–20188 (1994).

    CAS  PubMed  Google Scholar 

  10. Maeda, N., Niinobe, M., Inoue, Y. & Mikoshiba, K. Devl Biol. 133, 67–76 (1989).

    Article  CAS  Google Scholar 

  11. Llinas, R. & Sugimori, M. J. Physiol., Lond. 305, 171–195 (1980).

    Article  CAS  Google Scholar 

  12. Crepel, F. & Penit-Soria, J. J. Physiol., Lond. 372, 1–23 (1986).

    Article  CAS  Google Scholar 

  13. Eccles, J. C., Ito, M. & Szentagothal, J. The Cerebellum as a Neuronal Machine (Springer, Berlin. 1967).

    Book  Google Scholar 

  14. Llano, I., Marty, A., Armstrong, C. M. & Konnerth, A. J. Physiol., Lond. 434, 183–213 (1991).

    Article  CAS  Google Scholar 

  15. Aiba, A. et al. Cell 79, 377–388 (1994).

    Article  CAS  Google Scholar 

  16. Konnerth, A., Llano, I. & Armstrong, C. M. Proc. natn. Acad. Sci. U.S.A 87, 2662–2665 (1990).

    Article  ADS  CAS  Google Scholar 

  17. Lyon, M. F. & Searle, A. G. Genetic Variants and Strains of the Laboratory Mouse, 2nd edn (Oxford Univ. Press, 1989).

    Google Scholar 

  18. Yagi, T. et al. Proc. natn. Acad. Sci. U.S.A. 87, 9918–9922 (1990).

    Article  ADS  CAS  Google Scholar 

  19. Maeda, N., Niinobe, M., Nakahira, K. & Mikoshiba, K. J. Neurochem. 51, 1724–1730 (1988).

    Article  CAS  Google Scholar 

  20. Furuichi, T. et al. Nature 342, 32–38 (1989).

    Article  ADS  CAS  Google Scholar 

  21. Maeda, N., Niinobe, M. & Mikoshiba, K. EMBO J. 9, 61–67 (1990).

    Article  CAS  Google Scholar 

  22. Miyawaki, A., Furuichi, T., Maeda, N. & Mikoshiba, K. Neuron 5, 11–18 (1990).

    Article  CAS  Google Scholar 

  23. Nakade, S., Maeda, N. & Mikoshiba, K. Biochem. J. 277, 125–131 (1991).

    Article  CAS  Google Scholar 

  24. Nagata, E. et al. Neuroscience 61, 983–990 (1994).

    Article  CAS  Google Scholar 

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Matsumoto, M., Nakagawa, T., Inoue, T. et al. Ataxia and epileptic seizures in mice lacking type 1 inositol 1,4,5-trisphosphate receptor. Nature 379, 168–171 (1996). https://doi.org/10.1038/379168a0

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