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The microglial transcriptome of a novel murine model of Alzheimer's Disease: FACS-isolated microglia from heterozygous and homozygous App-SAA mice and WT littermate controls.

ABSTRACT: We created a novel murine model of Alzheimer's Disease using a knock-in strategy to humanize the sequence of the murine App gene and introduced three familial AD (FAD) mutations, Swedish (Swedish (KM670/671NL), Arctic (E693G)) and Austrian (T712I). We characterized the effects of these genetic modifications on the transcriptome of FACS-isolated microglia from 8-month-old App-SAA mice. Numerous genes were differentially expressed between cells from homozygous App-SAA animals compared to those from WT littermates. For example, we observed up-regulation of Disease-associated microglia (DAM) genes. In contrast, the transcriptome of microglia from heterozygous App-SAA animals broadly resembles that of their WT counterparts.

ORGANISM(S): Mus musculus

PROVIDER: GSE158152 | GEO | 2021/01/20

REPOSITORIES: GEO

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The microglial transcriptome of a novel murine model of Alzheimer's Disease: phagocytically active and inactive microglia from homozygous App-SAA mice and WT littermate controls.

Project description:We created a novel murine model of Alzheimer's Disease using a knock-in strategy to humanize the sequence of the murine App gene and introduced three familial AD (FAD) mutations, Swedish (Swedish (KM670/671NL), Arctic (E693G)) and Austrian (T712I). To determine whether App-SAA microglia exhibit cellular dysfunctions and whether these dysfunctions relate to fibrillar Ab internalization, mice were intraperitoneally (i.p.) injected with 10 mg/kg methoxy-X04. 24 hours after injection, mice were perfused with PBS, cortical and hippocampal tissues were dissected and processed into single-cell suspension and methoxy-X04-negative and methoxy-X04-positive microglia were isolated using FACS. Mirroring our gene expression studies, we found profound alterations of the AppSAA microglia transcriptome; these changes were exacerbated in methoxy-X04 positive compared to negative cells.

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Expression data from Hdac1 and 2 knock out microglia in 5X familial Alzheimer's disease (FAD) background

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The microglial transcriptome of a novel murine model of Alzheimer's Disease: phagocytically active and inactive microglia from homozygous App-SAA mice and WT littermate controls.

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Brain proteome analysis of APPswe mouse model at the early stages of Alzheimer's disease pathology

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Total RNA Sequencing in microglia isolated from N-AS treated APP/PS1 mice

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Role of Microglial C5aR1 in the Arctic Alzheimer’s Disease Mouse Model

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