LysM-Cre significantly reduced progranulin immunolabeling in microglia located in the corpus callosum (A, B, chi-square, p < 0.0001, n = 398 microglia from 5 Cre– mice and 285 microglia from 5 LysM-Cre+ mice). However, LysM-Cre failed to significantly reduce total brain progranulin protein (C, ANOVA effect of LysM-Cre, p = 0.2075, n = 10–17 mice per group) or RNA (D, ANOVA effect of genotype, p = 0.7602, n = 3–13 mice per group). In contrast, LysM-Cre reduced plasma progranulin levels by around 25% (E, t test, p = 0.0019, n = 20–22 mice per group). In A, progranulin immunostaining is shown in grayscale next to merged progranulin/Iba1 images. Scale bars in A represent 20 µm. FC = frontal cortex, Thal = thalamus. ** = p < 0.01 by t test, **** = p < 0.0001 by Chi-square test.