Extended Data Fig. 3. Triplication of the Ifnr locus drives increased IFNR protein expression and an aberrant antiviral response in a mouse model of Down syndrome.
a, Relative geometric mean fluorescent intensities (gMFIs) for IL10RB protein on CD45 + white blood cells (WBCs) from heterozygous Ifnr knockout mice (WT1xIfnrs, n = 14, 3 male, 11 female), wild-type (WT, n = 17, 7 male, 10 female), Dp16 (n = 15, 7 male, 8 female), and Dp162xIfnrs (n = 15, 8 male, 7 female), by flow cytometry. b, Soluble IFNAR2 protein by ELISA in the plasma of each biological replicate relative to the average WT value per experiment. The number of animals per group are the following: n = 28 WT1xIfnrs, n = 30 WT; n = 13 Dp16, and n = 26 Dp162xIfnrs (undocumented sex ratio). c, Example histogram for IFNR proteins on WBCs by flow cytometry. d, Pseudo-colored plot of gating strategy for immune subsets in whole blood by flow cytometry. Areas of high relative population density shown in red and orange, mid density in yellow, and low density in green and blue. e, IFNR protein expression on immune subsets isolated as in (d) from CD45 + WBCs. Heatmap indicates relative fluorescent intensities (RFIs) for gMFIs of the indicated genotype over the WT average IFNR gMFI per experiment. Gray denotes IFNRs not detected above isotype background. The number of animals is the same as for panel a. f, Representative histograms with gMFIs indicated for phosphorylated STAT1 (pSTAT1) by flow cytometry of WBCs at baseline or after stimulation with IFNα (10,000 U/mL) or IFNγ (100 U/mL) for 30 minutes. g, Cytokine levels in the plasma of mice treated with poly(I:C). Heatmap indicates log2 fold-change (FC) of cytokine protein in plasma of the indicated cohort +poly(I:C) relative to the WT poly(I:C) cohort after 3 days of the poly(I:C) regimen. WT poly(I:C) (n = 7, 3 male, 4 female), Dp16 poly(I:C) (n = 6, 5 male, 1 female), and Dp162xIfnrs poly(I:C) (n = 6, 3 male, 3 female). In a-b, each dot represents an independent biological animal replicate with the mean indicated with a dash. For a-b, e, and g, significance (*p < 0.05) and exact p-values were determined by a two-sided Mann Whitney test.