| Project/Area Number |
04558011
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Laboratory animal science
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| Research Institution | Hokkaido University |
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Principal Investigator |
ITAKURA Chitoshi Professor , Faculty of Veterinary Medicine, Hokkaido Univ., 獣医学部, 教授 (30021695)
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| 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)
小原 收 塩野義製薬(株), 研究所, 研究員
御領 政信 北海道大学, 獣医学部, 助教授 (80153774)
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| Project Period (FY) |
1992 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥18,900,000 (Direct Cost: ¥18,900,000)
Fiscal Year 1994: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1993: ¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 1992: ¥9,700,000 (Direct Cost: ¥9,700,000)
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| Keywords | QUAIL / NEUROFILAMENT / CYTOSKELETON / NERVE FIBER / AXONOPATHY / NEUROPATHOLOGY / ANIMAL MODEL / ACRYLAMIDE / 神経疾患 / 軸索 / ニューロフィラメント欠損 / ミュータントウズラ / ニューロフィラメントサブユニット / 振戦 |
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| 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
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