Tg2576小鼠的行为和病理特征观察
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摘要
目的针对阿尔茨海默症(AD)研究中常用的具有C57BL/6和SJL杂交背景的Tg2576转基因小鼠,初步探讨长期繁殖可能对该小鼠AD表型产生的影响。方法选取本实验室引进并长期繁育使用的Tg2576小鼠种群,利用Morris水迷宫、免疫组织化学、酶联免疫吸附法(ELISA)和免疫荧光技术,研究大鼠AD行为和病理表型。结果与对照小鼠相比,长期传代繁育的Tg2576小鼠随着年龄的增长,在水迷宫测试中仍然出现学习记忆能力的显著下降;免疫组织化学结果显示,小鼠脑皮层出现典型的β淀粉样蛋白(Aβ)沉积,且Aβ在脑组织中的含量较野生型小鼠显著升高;免疫荧光分析表明,在皮层Aβ斑块周围出现大量星形胶质细胞聚集的现象。结论长期繁育的Tg2576小鼠仍具有AD小鼠典型的疾病临床和病理特征。
Objective Tg2576 transgenic mice with C57 BL/6 and SJL hybridization background,which are commonly used in research of Alzheimer's disease(AD), were used to investigate the potential effect of long-term breeding on the phenotype of AD. Methods Utilizing Morris water maze, immunohistochemistry, ELISA and immunofluorescence, the behavior and pathological phenotype of AD were studied in these Tg2576 mice which were introduced and bred in our laboratory for a long time. Results With the age increase, the learning and memory ability of in these Tg2576 mice was still significantly decreased. The typical beta amyloid(Aβ) deposition was also found in the cerebral cortex of these mice by immunohistochemistry. The content of Aβ in brain tissue was significantly higher than that in control mice. In addtion, the immunofluorescence analysis indicated that a large number of astrocytes gathered around Aβ plaques in the cerebral cortex.Conclusion The long-term bred of Tg2576 mice still have the typical clinical and pathological characteristics of AD mice.
Objective Tg2576 transgenic mice with C57 BL/6 and SJL hybridization background,which are commonly used in research of Alzheimer's disease(AD), were used to investigate the potential effect of long-term breeding on the phenotype of AD. Methods Utilizing Morris water maze, immunohistochemistry, ELISA and immunofluorescence, the behavior and pathological phenotype of AD were studied in these Tg2576 mice which were introduced and bred in our laboratory for a long time. Results With the age increase, the learning and memory ability of in these Tg2576 mice was still significantly decreased. The typical beta amyloid(Aβ) deposition was also found in the cerebral cortex of these mice by immunohistochemistry. The content of Aβ in brain tissue was significantly higher than that in control mice. In addtion, the immunofluorescence analysis indicated that a large number of astrocytes gathered around Aβ plaques in the cerebral cortex.Conclusion The long-term bred of Tg2576 mice still have the typical clinical and pathological characteristics of AD mice.
引文
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[10] Unger C, Svedberg MM, Yu WF, et al. Effect of subchronic treatment of memantine, galantamine, and nicotine in the brain of Tg2576(APPswe)transgenic mice[J]. J Pharmacol Exp Ther, 2006, 317(1):30-36.
[2] Silver L. Encyclopedia of Genetics[M]. New York:Academic Press:2001:680.
[3] Bilkei-Gorzo A. Genetic mouse models of brain ageing and Alzheimer’s disease[J]. Pharmacol Ther, 2014, 142(2):244-257.
[4]李国营,张革,胡金家,等. APPSWE转基因鼠的繁育及子代鉴定的研究[J].中国病理生理杂志, 2004(1):114-117.
[5] Lassalle JM, Halley H, Daumas S, et al. Effects of the genetic background on cognitive performances of TG2576mice[J]. Behav Brain Res, 2008, 191(1):104-110.
[6] Alexander G, Hanna A, Serna V, et al. Increased aggression in males in transgenic Tg2576 mouse model of Alzheimer’s disease[J]. Behav Brain Res, 2011, 216(1):77-83.
[7]李国营,汪华侨,胡金家,等. AD转基因模型Tg2576鼠阳性子鼠的病理和认知行为变化[J].神经解剖学杂志,2006(4):384-388.
[8] Frautschy SA, Yang F, Irrizarry M, et al. Microglial response to amyloid plaques in APPsw transgenic mice[J].Am J Pathol, 1998, 152(1):307-317.
[9] Dong H, Csernansky CA, Martin MV, et al. Acetylcholinesterase inhibitors ameliorate behavioral deficits in the Tg2576 mouse model of Alzheimer’s disease[J]. Psychopharmacology(Berl), 2005, 181(1):145-152.
[10] Unger C, Svedberg MM, Yu WF, et al. Effect of subchronic treatment of memantine, galantamine, and nicotine in the brain of Tg2576(APPswe)transgenic mice[J]. J Pharmacol Exp Ther, 2006, 317(1):30-36.