A high-resolution linkage map of the tight skin 2 (Tsk2) locus: a mouse model for scleroderma (SSc) and other cutaneous fibrotic diseases

Tsk2/+ is a novel mutation that first appeared in the offspring of a male from the 101/H strain that had been administered the mutagenic agent, ethylnitrosourea. The mouse was recognized because of the tight skin in the interscapular region. In contrast to the Tsk mutation, which is known to reside on Chromosome (Chr) 2, the Tsk2 mutation has been localized to mouse Chr 1 by linkage studies to two visible Chr 1 mutations and three microsatellite markers. Like the Tsk mutation, the Tsk2 mutation is inherited as an autosomal dominant trait and leads to the development of a "tight skin" phenotype, which becomes apparent at 2 weeks of age. Histologic examination of skin samples from affected Tsk2 animals showed thickening of the dermis and excessive deposition of thick collagen fibers extending into the subdermal adipose tissue. Biochemical studies showed increased amounts of collagen and an increase in the steady state level of alpha 1 (1) procollagen mRNA in Tsk2 skin compared with normal skin.