Proteome analysis in mice expressing P301L tau

表达 P301L tau 的小鼠的蛋白质组分析

• 批准号: 6844690
• 负责人: IRVING E VEGA
• 金额: $ 4.53万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-01-01 至 2005-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6844690
• 关键词: SDS polyacrylamide gel electrophoresis; brain; genetically modified animals; laboratory mouse; mass spectrometry; neural degeneration; neuropathology; phenotype; phosphopeptides; phosphorylation; posttranslational modifications; protein localization; protein structure function; proteomics; spinal cord; tau proteins

DESCRIPTION (provided by applicant): The use of proteome analysis in disease investigations has been instrumental for the study of tissue, subcellular compartments, and even protein complexes in the quest to identify biomarkers for the diagnosis and early detection of several diseases. We intend to employ this high throughput technology in the analysis of tau and other proteins during the development of tauopathy in the FTDP-17 mouse model JNPL3, which expresses the human 4RON tau isoform bearing the P301L missense mutation. Previous studies demonstrated that in FTDP-17 P301L tau proteins undergo age- and pathological-dependent hyperphosphorylation, suggesting that aberrant tau phosphorylation may play an important role in the onset and/or progression of tauopathy. Furthermore, preliminary results in our laboratory showed that several proteins are differentially expressed between JNPL3 and non-transgenic littermates. In order to further characterize these changes mass spectroscopy-based phosphopeptide analysis will be employed in the quest to identify tau phosphorylation events at different stages in the development of tauopathy in the JPNL3 mice. In addition, a proteome analysis of fractionated proteins from brain and spinal cord tissues will be used for the identification, and subsequent characterization of proteins involved in and/or affected by tau aggregation. These approaches may contribute to the identification of important biological markers involved at early stages of the development of tauopathy and may bring insights into the molecular mechanism underline tau aggregation

描述（由申请人提供）：蛋白质组分析在疾病研究中的应用对于组织、亚细胞区室甚至蛋白质复合物的研究至关重要，以寻找用于诊断和早期检测多种疾病的生物标志物。我们打算在FTDP-17小鼠模型JNPL 3中tau蛋白病的发展过程中采用这种高通量技术分析tau蛋白和其他蛋白，JNPL 3表达携带P301 L错义突变的人4 RON tau同种型。先前的研究表明，在FTDP-17 P301 L tau蛋白经历年龄和病理依赖性的过度磷酸化，这表明异常的tau磷酸化可能在tau蛋白病的发生和/或进展中起重要作用。此外，我们实验室的初步结果表明，JNPL 3和非转基因同窝仔之间的几个蛋白质的差异表达。为了进一步表征这些变化，将采用基于质谱的磷酸肽分析来鉴定JPNL 3小鼠中tau蛋白病发展中不同阶段的tau磷酸化事件。此外，来自脑和脊髓组织的分级蛋白质的蛋白质组分析将用于鉴定和随后表征涉及tau聚集和/或受tau聚集影响的蛋白质。这些方法可能有助于鉴定在tau蛋白病发展的早期阶段涉及的重要生物标志物，并可能深入了解tau蛋白聚集的分子机制

项目成果

Phosphorylated p38MAPK specific antibodies cross-react with sarkosyl-insoluble hyperphosphorylated tau proteins.

磷酸化 p38MAPK 特异性抗体与肌氨酰不溶性过度磷酸化 tau 蛋白发生交叉反应。

• DOI: 10.1111/j.1471-4159.2004.02558.x
• 发表时间: 2004
• 期刊: Journal of neurochemistry
• 影响因子: 4.7
• 作者: Sahara,Naruhiko;Vega,IrvingE;Ishizawa,Takashi;Lewis,Jada;McGowan,Eileen;Hutton,Michael;Dickson,Dennis;Yen,Shu-Hui
• 通讯作者: Yen,Shu-Hui