Tight skin mouse subcutaneous hypertrophy can occur in the absence of alphabeta T cell receptor-bearing lymphocytes.

Abstract

The tight skin (TSK) mouse has been proposed to be a murine model for heritable fibrotic disorders, and studies have implicated immune dysregulation in TSK pathogenesis. We evaluated the core features of TSK cutaneous pathology to ascertain whether cutaneous features were altered in TSK mice deficient in alphabeta T cell receptor (TCR)-bearing lymphocytes. Blinded qualitative evaluations of cutaneous and subcutaneous tissues were performed to determine the effect of the TSK mutation and whether the TCR-alpha-/- mutation had any influence on TSK mediated pathology. Analysis by light microscopy revealed no difference in the thickness or any obvious changes in dermal architecture in 2 to 4-month-old TSK mice compared to age and sex matched littermate controls. The most consistent feature of TSK dermatohistopathology is the substantially expanded superficial fascia with accentuated "lamellar" architecture. We found that this reliable pathological marker and the characteristic skin tightness were not abrogated when the TSK mutation was crossed onto the TCR-alpha-/- background. The results dispute assertions that cutaneous and subcutaneous sclerosis in the TSK mouse are dependent upon the presence of CD4+ cells and that skin tightness can be dissociated from these pathological changes.