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.

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. This experiments examines FACS-isolated microglia from 18 mice from three genetic backgrounds (N = 6 WT, N =6 heterozygous App-SAA and N = 6 homozygous App-SAA animals). Microglia were isolated from the brain (cortex & hippocampus) of each animal using FACS and gene expression changes were analyzed using 3-tag RNA-seq. From each mouse, two (technical) replicate pools of microglia were collected and processed into separate libraries (library_replicate).