Fig. 5: Microglial Tbk1 deletion is sufficient to induce an FTD-like social recognition deficit.

a Workflow of the 3-chamber test to assess presence of sociability and social recognition (social novelty preference) defects in 4-month-old male mice with microglial specific deletion of one (Tbk1-µG-HET) or two (Tbk1-µG-KO) Tbk1 copies and compared to control littermates (Tbk1-µG-WT). Created in BioRender. Lenoel, I. (2025) https://BioRender.com/ct8qnd6. b Interaction times during the first three trials (trials 1–3) of the 3-chamber test (sociability phase). n = 12 mice per genotype (males only). Adjusted p values are indicated and were determined by a two-tailed type II Wald chi-square test with Tukey’s post hoc test. Results from trials 1–3 indicate no impairment of social interaction (sociability) due to microglial Tbk1 deletion. c Representative heatmaps of the mouse positions during the social recognition phase of the 3-chamber test (trial 4), shown for Tbk1-µG-KO and control Tbk1-µG-WT mice. d During trial 4, contact durations to stranger 1 (S1, known) and stranger 2 (S2, unknown) were measured. n = 12 mice per genotype. Adjusted p values are indicated and were determined by repeated measures two-way ANOVA with Sidak’s multiple comparisons test. e Calculation of the social recognition index (trial 4) per mouse. n = 12 mice per genotype. Adjusted p values are indicated and were determined by a two-tailed one sample t-test to the theoretical mean of 50%. Results from trial 4 (social recognition phase) indicate an impairment of social recognition due to microglial Tbk1 deletion. Of note, the observed social recognition (social novelty preference) deficit affects social memory, but spatial memory was unaffected (Supplementary Fig. 8e–g). d, e Data are shown as single data points and (b, d, e) means ± SEM. ns: not significant.