Fig. 1.

Grn^+/−:Tmem106b^+/− Exhibit a 40–50% Reduction in Both Progranulin and Tmem106b Protein Levels. In the frontal cortex of 5–6 month-old mice, the knockout Grn and Tmem106b alleles mediated the expected reduction of Tmem106b (a, ANOVA effect of Tmem106b, p < 0.0001) and progranulin (b, ANOVA effect of Grn, p < 0.0001) protein levels. Similar results were obtained in the hippocampus, with the expected reduction of Tmem106b (c, ANOVA effect of Tmem106b, p < 0.0001) and progranulin (d, ANOVA effect of Grn, p < 0.0001). Tmem106b (e, ANOVA effect of Tmem106b, p < 0.0001) and progranulin (f, ANOVA effect of Grn, p < 0.0001) were also reduced in the frontal cortex of 12 month-old mice. In all cases, the knockout Grn and Tmem106b alleles reduced their target protein levels by ~ 35–45% regardless of the genotype of the other allele. * = p < 0.05, ** = p < 0.01, *** = p < 0.001, **** = p < 0.0001 by Tukey’s post-hoc test. n = 5–12 mice per group for 5- to 6-month-old mice and 10–11 per group for 12-month-old mice