RT Journal Article SR Electronic T1 Expression of a constitutively active human STING mutant in hematopoietic cells produces an Ifnar1-dependent vasculopathy in mice JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e201800215 DO 10.26508/lsa.201800215 VO 2 IS 3 A1 Martin, Gary R A1 Henare, Kimiora A1 Salazar, Carolina A1 Scheidl-Yee, Teresa A1 Eggen, Laura J A1 Tailor, Pankaj P A1 Kim, Jung Hwan A1 Podstawka, John A1 Fritzler, Marvin J A1 Kelly, Margaret M A1 Yipp, Bryan G A1 Jirik, Frank R YR 2019 UL http://www.life-science-alliance.org/content/2/3/e201800215.abstract AB STING-associated vasculopathy with onset in infancy (SAVI) is an autoinflammatory disorder characterized by blood vessel occlusions, acral necrosis, myositis, rashes, and pulmonary inflammation that are the result of activating mutations in the STimulator of Interferon Genes (STING). We generated a transgenic line that recapitulates many of the phenotypic aspects of SAVI by targeting the expression of the human STING-N154S–mutant protein to the murine hematopoietic compartment. hSTING-N154S mice demonstrated failure to gain weight, lymphopenia, progressive paw swelling accompanied by inflammatory infiltrates, severe myositis, and ear and tail necrosis. However, no significant lung inflammation was observed. X-ray microscopy imaging revealed vasculopathy characterized by arteriole occlusions and venous thromboses. Type I interferons and proinflammatory mediators were elevated in hSTING-N154S sera. Importantly, the phenotype was prevented in hSTING-N154S mice lacking the type I interferon receptor gene (Ifnar1). This model, based on a mutant human STING protein, may shed light on the pathophysiological mechanisms operative in SAVI.