Deficiency of the Tangier Disease Gene Abca1 Is Associated With Microglial Defects in Mice

Microglia, the resident macrophages of the central nervous system, are a diverse population that develop during embryonic and postnatal stages in the mouse. Several signalling pathways are involved in their specification and maturation, but other types of cues might be involved, including lipid metabolism. Here, we evaluated the effect of the inactivation of two main cholesterol transporters in mice, ABCA1 and SR-B1, on microglial development. Using public datasets, we showed that both transporters are expressed in microglia and are differentially regulated in neurodegeneration models. Inactivation of either transporter was associated with distinct effects on microglial density and/or morphology at different developmental stages and in different brain regions. These studies suggest that microglia require appropriate lipid transport to support their homeostatic identity and could implicate this process in neurodegenerative diseases.