RNA-seq to investigate sex-dependent changes in microglia in Cst7 knockout mice crossed with a mouse model of amyloid-driven Alzheimer's Disease

Microglial endolysosomal dysfunction is strongly implicated in neurodegeneration. Transcriptomic studies show that a microglial state characterised by a set of genes involved in endolysosomal function is induced in both mouse Alzheimer's Disease (AD) models and in human AD brain, and that the onset of this state is emphasised in females. Cst7 (Cystatin F) is among the most highly unregulated genes in these microglia. However, the sex-specific function of Cst7 in neurodegenerative disease is not understood. Here, we crossed Cst7 -/- mice with the App NL-G-F mouse to test the role of Cst7 in a model of amyloid-driven AD.小胶质细胞内体溶酶体功能障碍（Microglial endolysosomal dysfunction）与神经退行性疾病的发生发展密切相关。转录组学研究显示，在小鼠阿尔茨海默病（Alzheimer's Disease, AD）模型与人类阿尔茨海默病脑组织中，均可诱导出以一系列参与内体溶酶体功能调控的基因为特征的小胶质细胞表型，且该表型的发生在雌性个体中更为显著。胱抑素F（Cystatin F，简称Cst7）是这类小胶质细胞中高度失调表达的基因之一。然而，目前尚不清楚胱抑素F在神经退行性疾病中的性别特异性功能。本研究将Cst7基因敲除（Cst7 -/-）小鼠与APP NL-G-F小鼠进行杂交，以探究胱抑素F在淀粉样蛋白驱动型阿尔茨海默病模型中的作用。