Objective: To describe the histopathologic and biochemical characteristics of skin from the Tsk2/+ mouse, a mutation with phenotypic features resembling those of systemic sclerosis (SSc), and to report the initial 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/+ mice and normal mice. An intersubspecific backcross was conducted as a first step toward identifying the position of the Tsk2 locus on mouse chromosome 1.
Results: Histologic examination of Tsk2/+ mouse skin revealed 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-state levels of alpha 1 (I) procollagen mRNA. Tsk2 was mapped to a 15.3-centimorgan interval on mouse chromosome 1.
Conclusion: Tsk2 is a novel mutation which displays histopathologic and biochemical abnormalities similar to those present in the skin of patients with SSc, including increased collagen content and expression of type I collagen genes. This mutation has been mapped to a 15.3-cM region on mouse chromosome 1. Further study of this novel mutation will allow the identification of previously undescribed mechanisms involved in the regulation of normal and pathologic collagen gene expression.