Aicardi–Goutières syndrome (AGS) is a rare monogenic autoinflammatory disease. It belongs to a group of autoimmune diseases desingnated as “Interpheronopathies”. These are characterized by a misregulated, constant over- production of antiviral type I interferons (IFN-I), which is caused by mutations in genes involved in nucleic acid metabolism or sensing. Amongst them are loss-of-function mutations of TREX1, SAMHD1, RNaseH2 and ADAR1 and gain-of-function (GOF) mutations of MDA5. 

Patients with RIG-I gain-of-function  (GOF) mutations develop type I interferonopathies such as Singleton-Merten syndrome and lupus nephritis. We have generated mice harbouring the human Singleton-Merten syndrome RIG-I disease variant E373A that spontaneously develop autoimmune symptoms.