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Demonstration of autoimmunity in the tight skin-2 mouse: a model for scleroderma
Journal article   Open access   Peer reviewed

Demonstration of autoimmunity in the tight skin-2 mouse: a model for scleroderma

Julieta Gentiletti, Laura J McCloskey, Carol M Artlett, Josephine Peters, Sergio A Jimenez and Paul J Christner
The Journal of immunology (1950), v 175(4), pp 2418-2426
15 Aug 2005
DOI: https://doi.org/10.4049/jimmunol.175.4.2418
PMID: 16081813
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.4049/jimmunol.175.4.2418View
Published, Version of Record (VoR) Open

Abstract

Autoimmune Diseases - physiopathology Antibodies, Antinuclear - biosynthesis Autoantigens - metabolism Age Factors Enzyme-Linked Immunosorbent Assay Humans Autoimmune Diseases - immunology Scleroderma, Systemic - genetics Male Scleroderma, Systemic - immunology Mice, Inbred C3H Autoimmune Diseases - genetics Mice, Inbred MRL lpr Animals Antibodies, Antinuclear - physiology Mice, Mutant Strains Scleroderma, Systemic - physiopathology Sex Factors Female Mice Antibodies, Antinuclear - metabolism Skinfold Thickness Fluorescent Antibody Technique, Indirect Disease Models, Animal
The tight skin-2 (Tsk2/+) mouse has been proposed as an animal model of systemic sclerosis (SSc) because this animal exhibits increased collagen synthesis and accumulation in the dermis. The Tsk2/+ mouse also has been reported to have a mononuclear cell infiltrate in the dermis; however, to date no evidence of autoimmunity has been described in this animal model. We report here that Tsk2/+ mice harbor numerous autoantibodies in their plasma including some, which are similar to those, present in SSc patients. Immunofluorescence with HEp-2 cells revealed the presence of anti-nuclear Abs (ANAs) in the plasma of 92% of the Tsk2/+ mice. In contrast, <5% of cage-mated CAST/ei mice had a positive ANA and none of the C3H/HeJ age-matched controls were positive. Homogenous, speckled, rim, nucleolar, centromere as well as combinations of these patterns were observed. The proportion of Tsk2/+ animals with a positive ANA increased slightly with age. ELISAs showed that 93% of the Tsk2/+ animals were positive for anti-Scl70, 82% for anti-centromere, 5% for anti-RNP/Sm, and none were positive for anti-RNA-polymerase II Abs. Indirect immunofluorescence with Crithidia luciliae and ELISA for anti-dsDNA Abs showed that 76% of Tsk2/+ mice were positive for this autoantibody. The high frequency of anti-Scl70 and anti-centromere autoantibodies indicates that Tsk2/+ mice display some humoral immune alterations which are similar to those found in patients with SSc. However, the Tsk2/+ mice also develop autoantibodies to dsDNA and a majority of the mice develop multiple autoantibody specificities (anti-Scl70, anti-CENP-B, and anti-dsDNA) indicating that the mouse may be a useful model to study autoimmunity in a wider spectrum of connective tissue diseases.

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Web of Science research areas
Immunology
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