title: Predictive parameters of joint disease in DBA/1 transgenic mice.
abstract: We recently reported an accelerated onset of collagen-induced arthritis in DBAII mice overexpressing a T cell receptor Valpha11.1/Vbeta8.2 transgene as a preclinical animal model for age-associated T cell dysfunction. The accelerated onset is due to a transgenically sensitized T cell population that reacts to bovine type 11 collagen without prior in vivo sensitization. The model presents a readily observable distal joint phenotype that would allow preliminary aging and intervention studies to be evaluated by monitoring the presence or absence or degree of phenotypic expression of disease. In order to characterize clinical signs, we evaluated 69 transgenic mice in six different experiments for anticollagen antibody levels, and assigned each a modified arthritic score based on the degree of redness or swelling of the digital joints. We also correlated these parameters with signs of distress, including weight bearing, activity levels, and body posture. The average onset of disease was consistently within a 28 to 35-day period. The average arthritic score at the time of onset was 8. We found that none of the parameters predicted the onset of joint disease, but the modified scoring system reflected the severity of joint disease and predicted the degree of distress associated with the acute inflammation. The ability to determine the severity of joint disease by gross physical examination is a useful clinical feature because a numerical score is reflective of the degree of inflammation. Because the transgenic mouse model is a T cell-driven disease, the effect of aging on T cell activity can be monitored easily. In addition, the use of our modified arthritic scoring system makes it possible to conduct mouse experiments in a humane manner.
authors.affiliation: Department of Comparative Medicine, School of Medicine, University of Washington, Seattle 98195, USA.
authors.forename: S
authors.initials: S
authors.lastname: Cheunsuk
authors.forename: E
authors.initials: E
authors.lastname: Gerken
authors.forename: G
authors.initials: G
authors.lastname: Osman
authors.forename: L
authors.initials: L
authors.lastname: Hood
authors.forename: W
authors.initials: W
authors.lastname: Ladiges
mesh_terms: D000375:Aging / Q000276:immunology*; D000818:Animals; D001168:Arthritis / Q000209:etiology*; D002417:Cattle; D003094:Collagen / Q000276:immunology; D051379:Mice; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta; D003094:Collagen