IFIH1 and systemic lupus erythematosus: Furthermore, constitutive activation of the MDA5-MAVS pathway by a gain-of-function mutation in MDA5 (G821S; Ifih1gs/+) causes a lupus-like autoimmune disease in mice [19]; MDA5 G821S mice display retarded growth, multi-organ pathology, and the majority die within six months of birth.