Dept of Translational Neuroscience, Michigan State University, Grand Rapids, MI, USA; School of Aging Studies, University of South Florida, Tampa, FL, USA.
Dept of Translational Neuroscience, Michigan State University, Grand Rapids, MI, USA.
Neurobiol Aging. 2023 Apr;124:39-50. doi: 10.1016/j.neurobiolaging.2022.06.014. Epub 2022 Dec 21.
Animal models of tauopathy help in understanding the role of mutations in tau pathobiology. Here, we used adeno-associated viral (AAV) vectors to administer three tau genetic variants (tau, tau, and tau) intracranially into 12-month-old C57BL/6Nia mice and collected tissue at 16 months. Vectors designed to express green fluorescent protein controlled for surgical procedures and exogenous protein expression by AAV. The tau genetic variants produced considerably different phenotypes. Tau and tau caused memory impairments. The tau caused increased amounts of aggregated tau, measured both neurochemically and histologically. Tau produced elevated levels of soluble tau and phosphorylated tau by ELISA and increased staining for phosphorylated forms of tau histologically. However, only the tau caused localized atrophy of brain tissue at the sites near the injection. The tau had low protein expression and produced no atrophy or memory impairments. This supports the potential use of AAV expressing tau in aged mice to examine events leading to neurodegeneration in Alzheimer's disease pathology.
神经tau 病变动物模型有助于了解 tau 病理生物学中突变的作用。在这里，我们使用腺相关病毒（AAV）载体将三种 tau 基因突变（tau、tau 和 tau）颅内注射到 12 个月大的 C57BL/6Nia 小鼠中，并在 16 个月时收集组织。设计用于表达绿色荧光蛋白的载体通过 AAV 控制手术程序和外源性蛋白表达。tau 基因突变产生了截然不同的表型。tau 和 tau 导致记忆障碍。tau 导致神经化学和组织学上测量的聚集 tau 量增加。tau 通过 ELISA 产生可溶性 tau 和磷酸化 tau 的升高水平，并在组织学上增加磷酸化 tau 形式的染色。然而，只有 tau 导致注射部位附近脑组织的局部萎缩。tau 的蛋白表达水平较低，不会导致萎缩或记忆障碍。这支持在老年小鼠中使用表达 tau 的 AAV 来检查导致阿尔茨海默病病理神经退行性变的事件。
