Type I IFN causes a dose-dependent microangiopathy. (A) Overview of experimental design (see text), with structure of the fusion gene used to generate the GFAP-IFN-α transgenic mice. (B) Scanning electron micrograph of IFN^High vascular cast, colored to show larger vessels (red) and microvasculature (box, yellow). (C-E) Hematoxylin and eosin sections of mice with maximal IFN overexpression show a spectrum of dose-dependent microangiopathic pathology, including endothelial hypertrophy and intimal thickening (C), microaneurysms (black arrows, D), and perivascular inflammatory cell infiltration and red bloods cells within narrowed lumen (blue arrows, E). Bars represent 20 μm. (F) Scanning electron micrograph of small vessel cast showing variation in microvessel caliber (white arrows). (G) Microvascular pathology in IFN-overexpressing mice is dose dependent. WT, wild type, no transgenic overexpression; IFN^Low, transgenic line with low IFN overexpression; IFN^High, transgenic line with high IFN overexpression (n = 8 mice per group). Data represent mean ± SEM; 1-way ANOVA, P < .001.