Proteome analysis in mice expressing P301L tau

描述(申请人提供)：在疾病调查中使用蛋白质组分析有助于研究组织、亚细胞室，甚至蛋白质复合体，以寻求识别用于诊断和早期发现几种疾病的生物标记物。我们打算将这项高通量技术应用于FTDP-17小鼠模型JNPL3的tau和其他蛋白质的分析，JNPL3表达带有P301L错义突变的人4RON tau亚型。以往的研究表明，在FTDP-17P301L中，tau蛋白发生了年龄和病理依赖性的过度磷酸化，提示tau蛋白的异常磷酸化可能在tau病的发生和/或发展中起重要作用。此外，我们实验室的初步结果表明，JNPL3和非转基因仔猪之间存在着几种蛋白质的差异表达。为了进一步确定这些变化的特征，基于质谱学的磷酸肽分析将被用来寻找在JPNL3小鼠tau异常发展的不同阶段的tau磷酸化事件。此外，来自大脑和脊髓组织的蛋白质组分析将用于鉴定参与和/或受tau聚集影响的蛋白质。这些方法可能有助于识别在互变发展的早期阶段涉及的重要生物标志物，并可能对支持tau聚集的分子机制有深入的了解。

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