Production of transgenic mice to analyze neuron specific toxicities of the intracellular domain of APP
| Project/Area Number |
20500334
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Shinshu University |
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Principal Investigator |
NAKAYAMA Kohzo Shinshu University, 医学部, 講師 (70192680)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | APP / Notch / アルツハイマー病 / γ-セクレターゼ / 脳・神経 / 神経科学 / 脳神経疾患 / 痴呆 / アルツハイマー / シグナル伝達 / 細胞内ドメイン / 細胞死 / アポトーシス / トランスジェニックマウス / DNAマイクロアレー |
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| Research Abstract |
Although amyloid precursor protein (APP) has a central role in Alzheimer's disease, the physiological functions of this protein are yet to be fully elucidated. We established an embryonic carcinoma P19 cell line expressing the intracellular domain of APP (AICD). While neurons were differentiated from these cell lines with retinoic acid treatment, expression of AICD induced neuron-specific apoptosis. We evaluated AICD-induced changes in gene expression through cell death. The expression of 41,256 transcripts was monitored by DNA microarray. The expression of 277 genes was induced more than 10-fold by the presence of AICD. Conversely, the expression of 341 genes was inhibited to less than one-tenth of the original level. These results suggest that AICD induces dynamic changes in gene expression, which may be closely correlated with AICD-induced neuron-specific apoptosis.
In addition, we are still producing transgenic mice to analyze neuron specific toxicities of the intracellular domain of APP leading to Alzheimer's disease.
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Report
(4 results)
Research Products
(20 results)
