Journals of Gerontology Series A: Biological Sciences and Medical Sciences, Vol 54, Issue 7 B271-B275, Copyright © 1999 by The Gerontological Society of America
Predictive parameters of joint disease in DBA/1 transgenic mice
S Cheunsuk, E Gerken, G Osman, L Hood and W Ladiges
Department of Comparative Medicine, School of Medicine, University of Washington, Seattle 98195, USA.
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.
