Predictive value of murine DTH arthritis for rheumatoid arthritis
Predictive value of murine DTH arthritis for rheumatoid arthritis (RA)
This project describes further development, refinement and mechanistic studies of an animal model in the field of rheumatology. The DTH-arthritis model was originally described by Tanaka et al.1.
The model builds on a transient footpad DTH reaction to a protein antigen, and induction of monoarthritis requires systemic administration of a sub-arthritogenic dose of anti-collagen type II (anti-CII) antibodies prior to elicitation of the footpad DTH reaction. We have successfully transferred the protocol to C57BL/6J mice 2, and have verified a monoarthritic phenotype characterized by cartilage destruction, bone erosion, hyperplasia, pannus formation and enhanced osteoclast activity, and demonstrated the involvement of both the innate (in particular neutrophils and macrophages) and the adaptive immune system (CD4+ T-cell dependent).
Importantly, in this model, the sequence of pathology-causing responses are synchronized even at the histological level; the disease incidence is 100%, intra-group variation is low and disease can be reduced both by preventive and therapeutic treatment with TNF-blocking drugs. Moreover, the ability to use the C57BL/6 strain greatly facilitates mode-of-action studies employing gene-knockout mice. Finally, we believe that the model could be modified to become relapsing-remitting, an important characteristic of human RA, which no existing animal model of RA mimics.
We hypothesize that this model can be utilized in an industrial setting to study the effect of new drug candidates in proof of concept studies and in mechanistic mode-of-action studies designed to reveal immunological aspects of arthritis-progressions in vivo. The project is thus excellently suited as a collaborative project between industry and university.
1. Tanaka D et al. , Clin Exp Immunology 148: 360-367, 2007., 2. Atkinson SM et al. Arthritis Res Ther. 2012 Jun 7;14(3)