Lysikova E A, Kuzubova E V, Radchenko A I, Patrakhanov E A, Chaprov K D, Korokin M V, Deykin A V, Gudyrev O S, Pokrovskii M V
Institute of Physiologically Active Compounds, Russian Academy of Sciences, Chernogolovka, 142432 Russia.
Belgorod State University, Belgorod, 308015 Russia.
Mol Biol (Mosk). 2023 Jan-Feb;57(1):85-94. doi: 10.31857/S0026898423010081.
Alzheimer's disease (AD) is the most common proteinopathy, which is accompanied by a steady decrease in the patient's cognitive functions with a simultaneous accumulation of amyloid plaques in brain tissues. Amyloid plaques are extracellular aggregates of amyloid β (Aβ) and are associated with neuroinflammation and neurodegeneration. Unlike humans and all other mammals, rats and mice do not reproduce AD-like pathology because there are three amino acid substitutions in their Aβ. Amyloid plaques form in the brains of transgenic mice with overexpression of human Aβ, and such mice are therefore possible to use in biomedicine to model the key features of AD. The transgenic mouse line APPswe/PS1dE9 is widely used as an animal model to study the molecular mechanisms of AD. A study was made to characterize the APPswe/PS1dE9/Blg subline, which was obtained by crossing APPswe/PS1dE9 mice on a CH3 genetic background with C57Bl6/Chg mice. No difference in offspring's survival and fertility was observed in the subline compared to wild-type control mice. Histological analysis of the brain in the APPswe/PS1dE9/Blg line confirmed the main neuromorphological features of AD and showed that amyloid plaques progressively increase in number and size during aging. The APPswe/PS1dE9/Blg line was assumed to provide a convenient model for developing therapeutic strategies to slow down AD progression.
阿尔茨海默病（AD）是最常见的蛋白质病，患者认知功能会持续下降，同时脑组织中会积累淀粉样斑块。淀粉样斑块是淀粉样β蛋白（Aβ）的细胞外聚集体，与神经炎症和神经退行性变有关。与人类和所有其他哺乳动物不同，大鼠和小鼠不会出现类似AD的病理变化，因为它们的Aβ中有三个氨基酸替换。在过度表达人Aβ的转基因小鼠大脑中会形成淀粉样斑块，因此这类小鼠可用于生物医学领域，以模拟AD的关键特征。转基因小鼠品系APPswe/PS1dE9被广泛用作研究AD分子机制的动物模型。本研究对APPswe/PS1dE9/Blg亚系进行了特征描述，该亚系是通过将CH3遗传背景的APPswe/PS1dE9小鼠与C57Bl6/Chg小鼠杂交获得的。与野生型对照小鼠相比，该亚系后代的存活率和生育力没有差异。对APPswe/PS1dE9/Blg品系小鼠大脑的组织学分析证实了AD的主要神经形态学特征，并表明随着年龄增长，淀粉样斑块的数量和大小会逐渐增加。APPswe/PS1dE9/Blg品系被认为是一种方便的模型，可用于开发减缓AD进展的治疗策略。
