Mouse model of autoinflammatory disease with dysfunction of intracellular DNA sensor system

Abstract

 COPA syndrome is an autoinflammatory disease, caused by heterozygous variants in the COPA gene. COPA syndrome patients present various manifestations such as interstitial lung disease and arthritis, accompanied with elevation of interferon-stimulated genes （ISGs） expression. COPA gene encodes the alpha subunit of the coatomer protein complex I （COP I）, which is a carrier complex required for retrograde protein trafficking from the Golgi apparatus to the endoplasmic reticulum. The detailed pathogenesis of the disease, however, is unknown and no treatment has been established. Several analyses using cell lines and model mice carrying the COPA syndrome gene variants have revealed that excessive activation of the intracellular DNA sensor pathway is involved in the pathogenesis of COPA syndrome. Here, we review recent findings on the pathogenesis of autoinflammatory diseases caused by dysfunction of the intracellular DNA sensor system, focusing on analyses using mouse models.