PT  - JOURNAL ARTICLE
AU  - Martin, Gary R
AU  - Henare, Kimiora
AU  - Salazar, Carolina
AU  - Scheidl-Yee, Teresa
AU  - Eggen, Laura J
AU  - Tailor, Pankaj P
AU  - Kim, Jung Hwan
AU  - Podstawka, John
AU  - Fritzler, Marvin J
AU  - Kelly, Margaret M
AU  - Yipp, Bryan G
AU  - Jirik, Frank R
TI  - Expression of a constitutively active human <em>STING</em> mutant in hematopoietic cells produces an <em>Ifnar1</em>-dependent vasculopathy in mice
AID  - 10.26508/lsa.201800215
DP  - 2019 Jun 01
TA  - Life Science Alliance
PG  - e201800215
VI  - 2
IP  - 3
4099  - http://www.life-science-alliance.org/content/2/3/e201800215.short
4100  - http://www.life-science-alliance.org/content/2/3/e201800215.full
SO  - Life Sci. Alliance2019 Jun 01; 2
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.