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1994 Fiscal Year Final Research Report Summary

Studies on neurofilament-deficient quails-an animal model for neuropathology

Research Project

Project/Area Number 04558011
Research Category

Grant-in-Aid for Developmental Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Laboratory animal science
Research InstitutionHokkaido University

Principal Investigator

ITAKURA Chitoshi  Professor , Faculty of Veterinary Medicine, Hokkaido Univ., 獣医学部, 教授 (30021695)

Co-Investigator(Kenkyū-buntansha) HAYASHI Masanobu  Professor, Faculty of Veterinary Medicine, Rakuno Univ., 獣医学科, 教授 (10130337)
KITAMURA Tadahisa  Research Director, Shionogi Research Laboratories, Shionogi & Co., Ltd., 研究所, 部長
MIZUTANI Makoto  Researcher, Nippon Institute for Biological Science., 実験動物研究所, 主任研究員 (40072467)
OCHIAI Kenji  Lecturer, Faculty of Veterinary Medicine, Hokkaido Univ., 獣医学部, 講師 (80214162)
Project Period (FY) 1992 – 1994
KeywordsQUAIL / NEUROFILAMENT / CYTOSKELETON / NERVE FIBER / AXONOPATHY / NEUROPATHOLOGY / ANIMAL MODEL / ACRYLAMIDE
Research Abstract

We discovered first a primary axonal disease affecting the central and peripheral nervous system in a new mutant strain of the Japanese quail, which was named Quv. This strain has no neurofilament (NF) in the axons or neuronal cell bodies in the whole body. This NF deficiency has never found in man and animals or birds.
To elucidate the biochemical mechanism of Quv in the present study, we examinated the in vivo expression of NF triplet protein subunits and the assembly state thereof in neuronal cell bodies in Quv and controls. Gel electrophoresis and Western blot analysis indicated that low, middle and high molecular mass NF subunits (NF-L,-M and -H) were markedly deficient in the central nervous system and sciatic nerve of Quv. Immunohistochemically, the spinal cord of Quv had no immunoreactive products corresponding to NF-L.However, NF-n and -H antisera stained few axons in the white matter and bounded to the ventral horn cell bodies, which in the control were not labeled. From these … More results, it was hypothesized that the deficiency of NFs in Quv results from an alteration of filament assembly caused by defective expression of NF-L.
IDPN (0.2g/kg body weight) was injected intraperitoneally into normal and Quv quails three times at every three days. The birds were necropsied on 10 to 12 days post-injection. Histologically, axonal swellings were observed in the ventral motoneurons, ventral root, commissura grisea and spinal ganglion in the spinal cord of the normal quails. Electron microscopically, the changes consisted of incereased NFs. In Quv injected with IDPN,no axonal changes were deteced. These findings suggest that IDPN attacks selectively NFs.
Acrylamide (100mg/kg body weight) was injected intraperitoneally into the quails at intervals of one day, which were necropsied after 10-30 injections. Axonal swellings with NF accumulation were found in normal quails. In Quv injected with acrylamide, no NF accumulation was revealed, but membranous organelles were increased in the nerve terminations. These findings indicated that acrylamide attacks primarily NFs as well as another sites in never fibers.
From our experiments, it is suggested that Quv quaills are available for neurological studies. Less

  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Yamasaki,H.et al.: "Hereditary hypotrophic axonopathy with neurofilament deficiency in a mutant strain of Japanese quail" Acta Neuropathologica. 82. 427-434 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamasaki,H.et al.: "Defective expression of neurofilament protein subunits in hereditary hypotrophic axonopathy of quail" Laboratory Investigation. 66. 734-743 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mizutani,M.et al.: "The hypotrophic axonopathy mutant in Japanese quail" Journal of Heredity. 83. 234-235 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 板倉智敏: "ニューロフィラメント欠損ウズラの開発について" 日生研たより. 38. 59-62 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sakaguchi,T.et al.: "Reduced diametr and conduction velocity of myelinated fibers in the sciatic nerve of a neurofilament-deficient mutant quail" Neuroscience Letters. 153. 65-68 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohara,O.et al.: "Neurofilament deficiency in quail caused by nonsense mutation in neurofilament-L gene" Journal of Cell Biology. 121. 387-395 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Zhao,J.X.et al.: "Smaller number of laege myelinated fibers and focal myelin thickening in mutant quails deficient in neurofilaments" Acta Neuropathologica. 86. 242-248 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mithuishi,K.et al.: "B,B'-iminodipropionitrile toxicity in normal and congenitally neurofilament-deficient Japanese quails" Acta Neuropathologica. 86. 578-581 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takahashi,A.et al.: "Acrylamide-induced neurotoxicity in the central nervous system of Japanese quails.Comparative studies of normal and neurofilamnt-deficient quails" Journal of Neuropathology and Experimental Neurology. 53. 276-283 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Zhao,J.X.et al.: "Greater number of microtubules per axon of unmyelinated fibers of mutant quails deficient in neurofilaments:Possible compensation for the absence of neurofilaments" Acta Neuropathologica. 87. 332-336 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hasegawa,H.et al.: "The monamine content of the brain in the neurofilament-deficient quails(the Quiver quail)" Biological and Pharmaceutical Bulletin. 7. 1053-1055 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takahashi,A.et al.: "Acrylamide-induced peripheral neuropathy in nomal and neurofilament-deficient Japanese quails" Acta Neuropathologica. 89. 17-22 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamasaki, H., Itakura, C.and Mizutani, M.: "Hereditary hypotrophic axonopathy with neurofilament deficiency in a mutant strain of the Japanese quail." Acta Neuropathol.82. 27-434 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamasaki, H., Bennett, G.S., Itakura, C.and Mizutani, M.: "Defective expression of neurofilamment protein subunits in hereditary hypotrophic axonopathy of quail." Lab.Invest.66. 734-743 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mizutani, M., Nunoya, T., Yamasaki, H.and Itakura, C.: "The hypotrophic axonopathy mutant in Japanese quail" J.Hered.83. 234-235 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sakaguchi, T., Okada, M., Kitamura, T.and Kawasaki, K.: "Reduced diametor and conduction velocity of myelinated fibers in the sciatic nerve of a neurofilament-deficient mutant quail." Neurosci.Lett.153. 65-68 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohara, O., Gahara, Y., Miyake, T., Teraoka, H.and Kitamura, T.: "Neurofilament deficiency in quail caused by nonsense mutation in neurofilament-L gene" J.Cell Biol.121. 387-395 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Zhao, J.X., Ohnishi, A., Itakura, C., Mizutani, M., Yamamoto, T., Hayashi, H.and Murai, Y.: "Smaller number of large myelinated fibers and focal myelin thickening in mutant quails deficient in neurofilaments." Acta Neuropathol.86. 242-248 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mitsuishi, K., Takahashi, A., Mizutani, M., Ochiai, K.and Itakura, C.: "beta, beta'-iminodipropionitrile toxicity in normal and congenitally neurofilament-deficient Japanese quail." Acta Neuropathol.86. 578-581 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi, A., Mizutani, M.and Itakura, C.: "Acrylamide-induced neurotoxicity in the central nervous system of Japanese quails. Comparative studies of normal and neurofilament-deficient quails" J.Neuropathol.Exp.Neurol.53. 276-283 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Zhao, J.X., Ohnishi, A., Itakura, C., Mizutani, M., Yamamoto, T., Hayashi, H.and Murai, Y.: "Greater number of microtubules per axon of unmyelinated fibers of mutant quails deficient in neurofilaments : Possible compensation for the absence of neurofilaments." Acta Neuropathol.87. 332-336 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hasegawa, H., Murayama, T., Takahashi, A., Itakura, C.and Nomura, Y.: "The monamine content of the brain in the neurofilament-deficient quails (the Quiver quail)." Biol.Pharma.Bull.7. 1053-1055 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi, A., Mizutani, M.and Itakura, C.: "Acrylamide-induced peripheral neuropathy in normal and neuro-filament-deficient Japanese quails." Acta Neuropathol.89. 17-22 (1995)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1996-04-15  

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