Correlation between the concentration of serum anti-topoisomerase I autoantibodies and histological and biochemical alterations in the skin of tight skin mice.

Cutaneous hyperplasia observed in tight skin mice is due to a mutation located on chromosome 2. While homozygous mice die in utero, the heterozygotes survive. TSK syndrome is associated with the presence of autoantibodies specific for scleroderma target autoantigens. The presence of autoantibodies specific for topoisomerase I is characteristic of both human and murine disease. We have generated two distinct genotypes of mice, TSK/+ and +/+ with respect to the TSK trait by breeding TSK mice with immunodeficient mouse strains. Since the mutated gene of TSK syndrome has not yet been cloned, only histological and biochemical criteria were used for defining TSK genotype. In the F1 mice derived by mating TSK/+ mice with RAG2-/-, JH-/-, or C57BLvit/vit mice, we have found a good correlation between the amount of serum anti-topoisomerase I autoantibodies present and the histopathological and biochemical alterations that are characteristic of TSK scleroderma-like syndrome.