Tight-Skin Mouse an Experimental Model for Scleroderma

Scleroderma is the third commonest inflammatory connective tissue disease affecting human. Based on the extent of sclerodermatous changes scleroderma comprises of two main groups: localized and generalized. The latter diffuse form, also known as systemic sclerosis, may be subdivided into two subgroups: (a) generalized (classical) disease in which there is extensive cutaneous and internal organ involvement, and (b) CREST syndrome with limited cutaneous and internal organ involvement. Sclerodermatous skin changes can be divided into three phases: edematous, indurative/sclerotic and atrophic phases. The edematous phase is characterized by increased synthesis of mucopolysaccharides within the affected tissues. Indurative phase is often characterized by increased synthesis and accumulation of collagen, destruction of dermal appendages and fibrosis of arterioles. The final atrophic phase is characterized by a decrease in the thickness of affected skin accompanied by atrophy of the underlying tissue. The striking feature of classical systemic sclerosis (referred to as SSc) is the occurrence of dermal fibrosis associated with vascular lesions and sclerotic changes in one or more internal organs like heart, lung, kidneys and gastrointestinal tract. Cellular infiltration of dermis with T and B lymphocytes, plasma cells, macrophages and fibroblastic type occur in 50% of patients. Thus, the outstanding features responsible for the clinical and pathological manifestations of the disease are: 1) increased synthesis and excessive deposition of collagen and other connective tissue macromolecules in the extracellular matrix of skin and target organs, 2) severe alterations in the microvasculature and, 3) inflammatory and autoimmune manifestations. Hypergammaglobulinemia and production of autoantibodies to various nuclear, nucleolar and connective tissue proteins are seen in 40-90% of SSc patients. The presence of serum autoantibodies specific for topoisomerase I (topo I), RNA polymerase I (RNA pol I), and fibrillarin is considered highly specific for this disease. At present, it is not clear whether the appearance of immunological abnormalities in SSc is an epiphenomenon or is related to its pathogenesis. Although recent advances in molecular biology and immunology helped identification of the target autoantigens involved in scleroderma, till now it has not been shown how the production of autoantibodies is related to the pathogenesis of this disease. Further, neither the e