Transcriptome analysis of the LPS response of BV-2 microglial cells displaying a CRISPR/Cas9-induced knockout of peroxisomal genes (Abcd1/Abcd2 or Acox1)
In X-linked adrenoleukodystrophy (X-ALD), the most common peroxisomal disorder, microglial defect is suggested to prime and amplify the neuroinflammatory process. By using CRISPR/Cas9 gene editing, we recently established BV-2 microglial cell models to study the impact of dysfunctional peroxisomal b-oxidation and demonstrated the emergence of a disease-associated microglial signature in these cell lines. Their transcriptomic analysis suggested consequences on immune response. To go further, we have used RNA-sequencing and functional assays related to immune response to compare the WT and mutant BV-2 cell lines in basal conditions or upon lipopolysaccharide (LPS) stimulation. Overall design: Three genotypes were included in the study: WT BV-2 cells and 2 mutant BV-2 cells (Abcd1/Abcd2 double-deficient, Acox1-deficient). See Raas et al. 2019, PMID: 30769094 and PMID: 30312667 for the description of the mutant cell lines. Cells were incubated in the presence or absence of 1 µg/ml  LPS during 24 h.