A microglial cell model for acyl-CoA oxidase 1 deficiency

Q Raas, F-E Saih, C Gondcaille, D Trompier, Y Hamon, V Leoni, C Caccia, B Nasser, M Jadot, F Ménétrier, G Lizard, M Cherkaoui-Malki, P Andreoletti, S Savary

Research output: Contribution to journalArticlepeer-review


Acyl-CoA oxidase 1 (ACOX1) deficiency is a rare and severe peroxisomal leukodystrophy associated with a very long-chain fatty acid (VLCFA) β–oxidation defect. This neurodegenerative disease lacks relevant cell models to further decipher the pathomechanisms in order to identify novel therapeutic targets. Since peroxisomal defects in microglia appear to be a key component of peroxisomal leukodystrophies, we targeted the Acox1 gene in the murine microglial BV-2 cell line. Using CRISPR/Cas9 gene editing, we generated an Acox1-deficient cell line and validated the allelic mutations, which lead to the absence of ACOX1 protein and enzymatic activity. The activity of catalase, the enzyme degrading H 2O 2, was increased, likely in response to the alteration of redox homeostasis. The mutant cell line grew more slowly than control cells without obvious morphological changes. However, ultrastructural analysis revealed an increased number of peroxisomes and mitochondria associated with size reduction of mitochondria. Changes in the distribution of lipid droplets containing neutral lipids have been observed in mutant cells; lipid analysis revealed the accumulation of saturated and monounsaturated VLCFA. Besides, expression levels of genes encoding interleukin-1 beta and 6 (IL-1β and IL-6), as well as triggering receptor expressed on myeloid cells 2 (Trem2) were found modified in the mutant cells suggesting modification of microglial polarization and phagocytosis ability. In summary, this Acox1-deficient cell line presents the main biochemical characteristics of the human disease and will serve as a promising model to further investigate the consequences of a specific microglial peroxisomal β–oxidation defect on oxidative stress, inflammation and cellular functions.

Original languageEnglish
Pages (from-to)567-576
Number of pages10
JournalBiochimica et biophysica acta. Molecular and cell biology of lipids
Issue number4
Early online date2018
Publication statusPublished - Apr 2019


  • Acyl-CoA oxidase
  • Microglia
  • Peroxisome
  • Cell Line
  • Acyl-CoA Oxidase/deficiency
  • Fatty Acids/metabolism
  • Cell Proliferation
  • Oxidative Stress
  • Hydrogen Peroxide/metabolism
  • Neurodegenerative Diseases/genetics
  • Microglia/cytology
  • Gene Editing
  • Animals
  • Models, Biological
  • CRISPR-Cas Systems
  • Fatty Acids, Unsaturated/metabolism
  • Mice
  • Mutation


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