Transcriptomic analysis of spinal cord microglial cells from NTg and ATXN2-Q33;TDP-43 adult mice
Intermediate-length repeat expansions in ATAXIN-2 (ATXN2) are a strong genetic risk factor for amyotrophic lateral sclerosis (ALS). At the molecular level, ATXN2 intermediate expansions enhance TDP-43 toxicity and pathology. However, whether this triggers ALS pathogenesis at the cellular and functional level remains unknown. Our study shows that  microglial cells might contribute to ALS-related pathology observed in mice carrying ATXN2 intermediate repeat expansions (Q33) in an ALS background (TDP-43). To investigate whether ATXN2-Q33;TDP-43 spinal cord microglia are transcriptomically different from non transgenic counterparts, we performed RNA sequencing of sorted microglial cells from knock-in (ATXN2-Q33;TDP-43) as well as non-transgenic (NTg) mice. Overall design: Microglial cells were isolated from 7-months-old spinal cords using CD11b-coated beads. A total of 9 animals per mouse line were used (ATXN2-Q33;TDP43 and NTg). Each sample consisted of 3 pooled spinal cord isolated microglia.