title: Tight skin 2 mice exhibit a novel time line of events leading to increased extracellular matrix deposition and dermal fibrosis.
abstract: 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-β1) 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-β1 over-production occurring at least two months before bona fide fibrosis, that is not dependent on ANA production.
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Kristen B
authors.initials: KB
authors.lastname: Long
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Carol M
authors.initials: CM
authors.lastname: Artlett
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USA. Electronic address: Eblanken@Drexelmed.edu.
authors.forename: Elizabeth P
authors.initials: EP
authors.lastname: Blankenhorn
mesh_terms: D000367:Age Factors; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D003094:Collagen / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology*; D005355:Fibrosis; D005455:Fluorescent Antibody Technique; D006909:Hydroxyproline / Q000378:metabolism; D016014:Linear Models; D051379:Mice; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D012595:Scleroderma, Systemic / Q000235:genetics* / Q000503:physiopathology*; D012867:Skin / Q000378:metabolism / Q000473:pathology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D053773:Transforming Growth Factor beta1; D003094:Collagen; D006909:Hydroxyproline
keywords: Collagen; Elastic fibers; Skin; Systemic sclerosis; Tight skin 2 mouse