| First Author | Long KB | Year | 2014 |
| Journal | Matrix Biol | Volume | 38 |
| Pages | 91-100 | PubMed ID | 24820199 |
| Mgi Jnum | J:215403 | Mgi Id | MGI:5605226 |
| Doi | 10.1016/j.matbio.2014.05.002 | Citation | Long KB, et al. (2014) Tight skin 2 mice exhibit a novel time line of events leading to increased extracellular matrix deposition and dermal fibrosis. Matrix Biol 38:91-100 |
| abstractText | The tight skin 2 (Tsk2) mouse model of systemic sclerosis (SSc) has many features of the human disease including tight skin, fibrosis, extracellular matrix abnormalities, and reported antinuclear antibodies (ANA). Here we report that Tsk2/+ mice develop excess dermal fibrosis with age, as skin is not significantly fibrotic until 10 weeks, a full eight weeks after the development of the physical tight skin phenotype. Concomitantly with the tight skin phenotype at two weeks of age, Tsk2/+ mice demonstrate increased levels of total transforming growth factor beta 1 (TGF-beta1) and excessive accumulation of dermal elastic fibers. The increase in elastic fibers is not responsible for tight skin, however, because Tsk2/+ mice genetically engineered to lack skin elastic fibers nevertheless have tight skin and fibrosis. Finally, about two months after the first measurable increases of total collagen, a portion of Tsk2/+ mice produce ANAs, but at a similar level to wild-type littermates. The timeline of disease development in the Tsk2/+ mouse shows that fibrosis is progressive, with elastic fiber alterations and TGF-beta1 over-production occurring at least two months before bona fide fibrosis, that is not dependent on ANA production. |
