Fig. 5: Triplication of the Ifnr locus promotes developmental delays and cognitive deficits in a mouse model of DS.
a, Odds ratio plots for developmental milestone achievement in neonates as assessed by mixed effects Cox regression for the indicated pairwise comparisons between Dp16, Dp162xIfnrs and WT animals, with adjustment for the covariates sex (fixed) and litter (random). Square points represent ‘success’ ratios with size proportional to −log10(q) and error bars corresponding to 95% CIs; red indicates q < 0.1 after Benjamini–Hochberg correction; vertical dashed lines indicate odds ratio of 1. Numbers of animals assessed for each milestone are shown in the table at right. b, Freezing behavior during CFC of adult WT (n = 33, 13 male and 20 female), Dp16 (n = 17, 8 male and 9 female) and Dp162xIfnrs (n = 23, 11 male and 12 female). Data are represented as means ± s.e.m., with significance determined by two-way repeated measures ANOVA and Tukey’s HSD test; asterisks indicate P < 0.05 and are colored by comparison—Dp16 versus WT (blue), Dp162xIfnrs versus WT (orange) and Dp16 versus Dp162xIfnrs (pink). See Source Data and Extended Data Fig. 5 for exact P values. c, Swim path efficiency of mice navigating to the escape platform in an MWM for male and female (M and F), WT (n = 39, 19 male and 20 female), Dp16 (n = 28, 13 male and 15 female) and Dp162xIfnrs (n = 25, 12 male and 13 female). Statistics as in b. d, Representative swim trials for males from block 9 in the MWM with platform location denoted for the acquisition (gray circle) and reversal (black circle) phases. e, Mouse target quadrant occupancy during reversal probe trial of MWM; data are represented as means ± s.e.m., with significance determined by one-way ANOVA and Dunnett’s correction. f, Heatmap displaying P values from IPA of transcriptome changes in brains from Dp16 versus WT animals, ranked by decreasing significance (right-tailed Fisher’s exact test, WT (n = 6, 2 male and 4 female), Dp16 (n = 5, 2 male and 3 female) and Dp162xIfnrs (n = 7, 4 male and 3 female). g, Heatmaps (top) representing median RPKM expression z scores per genotype and sina plots (bottom) for the example genes from the indicated pathways; q values determined by DESeq2, with significance set at q < 0.1.
