A syndrome resembling human systemic sclerosis (scleroderma) in MRL/lpr mice lacking interferon-gamma (IFN-gamma) receptor (MRL/lprgammaR-/-).

MRL/lpr mice develop a systemic autoimmune disease characterized by autoantibodies and inflammatory lesions in various organs. The main cause of early mortality is glomerulonephritis. We previously found that MRL/lprgammaR-/- mice are protected from glomerulonephritis and have an increased life span compared with their MRL/lprgammaR+/+ littermates. We now carried out a histopathological study of a selection of organs of MRL/lprgammaR-/- mice. Mice were killed as soon as they showed clinical signs of disease. In the majority of animals skin lesions were the first apparent pathology. Mononuclear cell infiltrates were frequent in skin, lungs and kidneys, and they occurred also in liver, salivary glands and heart. In infiltrated areas there was an abnormal accumulation of bundles of collagen. In the lungs of MRL/lprgammaR-/- mice, and occasionally in other organs, small and middle-sized arteries and veins showed intimal proliferation, resulting in a narrowed lumen. Alveolitis was widespread. Mononuclear cell infiltrates and excessive production of collagen in the skin and several visceral organs, thickening of vascular intima and autoantibodies are characteristic features of human systemic sclerosis. Thus, MRL/lprgammaR-/- mice might represent a model for that disease.