Modulation of cerebellar degeneration-associated gene in cultured cells and establishment of experimental model of paraneoplastic cerebellar degeneration
| Project/Area Number |
04670503
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurology
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| Research Institution | KANAZAWA MEDICAL UNIVERSITY |
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Principal Investigator |
SAKAI Koichiro Kanazawa Medical University Department of Neurology Assistant Professor, 医学部, 助教授 (70225754)
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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 |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1994: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1993: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1992: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | Paraneoplastic Syndromes / Limbic Encephalitis / Hippocampus / Autoantigen / Genome / 傍腫瘍性神経症候群 / 自己抗体 / cDNAクローニング / 小脳変性 / 抗神経細胞抗体 / 自己免疫 / 遺伝子導入 / 組換え体蛋白 / B細胞エピトープ / leucine zipper |
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| Research Abstract |
We immunized five different strains of mice with the recombinant human PCD17 protein, which is recognized by anti-Purkinje cell antibodies in the sera of patients with paraneoplastic cerebellar degeneration, and explored whether or not antibodies against cerebellar Purkinje cells could be induced in vivo. Autoantibodies against the cytoplasmic protein of Purkinje cells and other neurons were raised in all the strains of mice. The pattern of immunostaining seen with the mouse antisera is similar to that seen with the human PCD sera. The titers of the induced antibodies were comparable to or even higher than those of humans. The deposition of IgG also was demonstrated in the cytoplasm of Purkinje cells in the immunized mice. In spite of the generation of anti-Purkinje cell antibodies in vivo, neither clinical nor pathologic changes consistent with cerebellar degeneration have been detected 1 year following the first immunization.
In addition, we examined the antigenic region on PCD-17 by immunoblots with deletion fragment proteins of recombinant PCD17 protein, and found that a major epitope was determined on the amino acid residues in the leucine zipper motif.
A hippocampal 38 kd autoantigen recognized by an autoantibody from the serum of a patient with paraneoplastic limbic encephalitis and small cell lung carcinoma was isolated by screening a human hippocampal cDNA library. The 1,991-nucleotide ple21 clone was obtained and the deduced 350-residue protein cncoded by the ple21 cDNA clone was found to be highly homologous to the neuron-specific RNA recognition motifs-containing proteins.
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Report
(4 results)
Research Products
(14 results)
