Demonstration of autoimmunity in the tight skin-2 mouse: a model for scleroderma.
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.
Gentiletti
Julieta
J
Division of Rheumatology, Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.
McCloskey
Laura J
LJ
Artlett
Carol M
CM
Peters
Josephine
J
Jimenez
Sergio A
SA
Christner
Paul J
PJ
D000367:Age Factors; D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D001324:Autoantigens / Q000378:metabolism; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology* / Q000503:physiopathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D019463:Mice, Inbred MRL lpr; D008817:Mice, Mutant Strains; D012595:Scleroderma, Systemic / Q000235:genetics* / Q000276:immunology* / Q000503:physiopathology; D012737:Sex Factors; D012885:Skinfold Thickness
D000974:Antibodies, Antinuclear; D001324:Autoantigens