A human microglial cell model of autosomal recessive spastic ataxia of Charlevoix-Saguenay

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare disorder caused by loss-of-function mutations in the sacsin chaperone. Sacsin was initially described as a neuronal protein but is also found in astroglia and microglia. We developed and characterized a new microglial cell model of ARSACS based on human HMC3 cells. HMC3Sacs−/− cells show aberrant distribution of vimentin and mitochondrial networks, and other alterations with potential consequences on neuroinflammation. Our results support a possible role for microglial cells in ARSACS and provide a new tool to understand glial-specific mechanisms involved in this pathology.