Better genetic markers for microglia could aid the study of their physiological roles. Here, the authors generated mice in which transient Cre recombinase activity in cells expressing CX3CR1 (a chemokine receptor present in many myeloid-lineage cells) mediates the deletion of target genes. Four weeks after Cre activation, they observed stable target gene deletion in microglia but not in other CX3CR1-expressing cell populations that have a faster turnover rate. This approach allowed the authors to delete transforming growth factor-β-activated kinase 1 (TAK1; also known as MAP3K7) specifically in microglia and revealed that it acts to promote inflammatory gene expression and immune cell influx in a mouse model of autoimmune inflammation.