Tau P301S (Line PS19) 物种:小鼠基因:MAPT突变:MAPT*P301S编辑类型:MAPT - 转基因相关疾病:阿尔茨海默症、额颞叶痴呆品系名称:B6;C3-Tg(Prnp-MAPT*P301S)PS19Vle/J遗传背景: (C57BL/6 x C3H)F1基因编辑 PS19转基因小鼠表达突变的人类微管相关蛋白tau、MAPT,由小鼠朊蛋白 (Prnp)启动子驱动。该转基因体系编码与疾病相关的P301S突变,并包括四个微管结合结构域和一个N末端插入 (4R/1N)。转基因插入于Chr3:140354280-140603283 (Build GRCm38/mm10),导致249 Kb的缺失,不影响任何已知的基因 (Goodwin et al., 2017)。突变的人类tau的表达量是内源性小鼠蛋白的五倍 (Yoshiyama et al., 2007)。 相关品系 B6N.Cg-Tg(Prnp-MAPT*P301S)PS19Vle/J,The Jackson Lab Stock#024841; 冷冻保存。 参考资料 Jax资料:http://jaxmice.jax.org/strain/008169.html Alzforum资料:http://www.alzforum.org/research-models/tau-p301s-line-ps19 Goodwin LO, et al. Large-scale discovery of mouse transgenic integration sites reveals frequent structural variation and insertional mutagenesis.bioRχiv preprint first posted online Dec. 18, 2017 Holmes BB, et al. Proteopathic tau seeding predicts tauopathy in vivo. Proc Natl Acad Sci U S A. 2014 Oct 14;111(41):E4376-85. Epub 2014 Sep 26 Iba M, et al. Synthetic tau fibrils mediate transmission of neurofibrillary tangles in a transgenic mouse model of Alzheimer's-like tauopathy. J Neurosci. 2013 Jan 16;33(3):1024-37. Maruyama M, et al. Imaging of tau pathology in a tauopathy mouse model and in Alzheimer patients compared to normal controls. Neuron. 2013;79(6):1094-108. Takeuchi H, et al. P301S mutant human tau transgenic mice manifest early symptoms of human tauopathies with dementia and altered sensorimotor gating. PLoS One. 2011;6(6):e21050. Yoshiyama Y, et al. Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron. 2007 Feb 1;53(3):337-51. Zhang B, et al. The microtubule-stabilizing agent, epothilone D, reduces axonal dysfunction, neurotoxicity, cognitive deficits, and Alzheimer-like pathology in an interventional study with aged tau transgenic mice. J Neurosci. 2012 Mar 14;32(11):3601-11.