THE TIGHT-SKIN-2 MOUSE - AN ANIMAL-MODEL OF SCLERODERMA DISPLAYING CUTANEOUS FIBROSIS AND MONONUCLEAR CELL INFILTRATION

Objective. To describe the histopathologic and biochemical characteris tics of skin from the Tsk2/+ mouse, a mutation with phenotypic feature s resembling those of systemic sclerosis (SSc), and to report the init ial genetic mapping of the Tsk2 locus. Methods. Histologic examination was performed and collagen content and type I collagen messenger RNA (mRNA) levels were determined in skin biopsy specimens from Tsk2/+ mic e and normal mice. An inter-subspecific backcross was conducted as a f irst step toward identifying the position of the Tsk2 locus on mouse c hromosome 1. Results. Histologic examination of Tsk2/+ mouse skin reve aled marked accumulation of collagen and infiltration with mononuclear cells in the dermis and adipose tissue, Biochemical studies of Tsk2/ mouse skin showed increased collagen content and elevated steady-stat e levels of alpha 1(I) procollagen mRNA. Tsk2 was mapped to a 15.3-cen timorgan interval on mouse chromosome 1. Conclusion. Tsk2 is a novel m utation which displays histopathologic and biochemical abnormalities s imilar to those present in the skin of patients with SSc, including in creased collagen content and expression of type I collagen genes, This mutation has been mapped to a 15.3-cM region on mouse chromosome 1. F urther study of this novel mutation will allow the identification of p reviously undescribed mechanisms involved in the regulation of normal and pathologic collagen gene expression.