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

MRL/lpr mice develop a systemic autoimmune disease characterized by autoant ibodies and inflammatory lesions in various organs. The main cause of early mortality is glomerulonephritis. We previously found that MRL/lpr gamma R- /- mice are protected from glomerulonephritis and have an increased life sp an compared with their MRL/lpr gamma R+/+ littermates. We now carried out a histopathological study of a selection of organs of MRL/lpr gamma R-/- mic e. Mice were killed as soon as they showed clinical signs of disease. In th e majority of animals skin lesions were the first apparent pathology. Monon uclear cell infiltrates were frequent in skin, lungs and kidneys, and they occurred also in liver, salivary glands and heart. In infiltrated areas the re was an abnormal accumulation of bundles of collagen. In the lungs of MRL /lpr gamma R-/- mice, and occasionally in other organs, small and middle-si zed arteries and veins showed intimal proliferation, resulting in a narrowe d lumen. Alveolitis was widespread. Mononuclear cell infiltrates and excess ive production of collagen in the skin and several visceral organs, thicken ing of vascular intima and autoantibodies are characteristic features of hu man systemic sclerosis. Thus, MRL/lpr gamma R-/- mice might represent a mod el for that disease.