Graduation Year


Embargo Period


Document Type

Research Paper

Degree Name

Medical Doctor (MD)


Biomedical Sciences

First Advisor

Andrea Bottaro

Second Advisor

Igor Kuzin

Third Advisor

Bradford D. Fischer


Allergy and Immunology, Medical Research, Genetics


Rheumatoid arthritis (RA) is a chronic auto-inflammatory condition that affects multiple joints in the body, causing synovial thickening, joint swelling and significant bone erosion. The inflammatory effects of the disease are known to cause significant pain, disability and depression in many patients. Mouse models of RA, including a transgenic mouse model that over-expresses the inflammatory cytokine, TNF-α (i.e. the TNFtg mouse strain), have been used to explore the pathogenesis of RA. However, the role that TNF-α over-expression plays on behavior is understood poorly. The purpose of the present study was to quantify the progression of disease in TNFtg mice using two behavioral assays: the rotorod, and locomotor activity. The rotorod has been shown to be an effective method for the analysis of motor coordination, while locomotor activity has been an effective tool in assessing spontaneous ambulatory behavior. These data were compared to another study in which mechanical sensitivity was assessed. On both procedures, mice were tested from the age of 6 weeks to 18 weeks, in two-week increments. The data gathered showed a significant decrease in the time spent on the rotorod by the TNFtg mice compared to their wild type controls, and these effects emerged following 12 weeks of age. On locomotor activity, TNFtg mice had a significant decrease in ambulatory behavior compared to their wild type controls with significant effects also emerging after 12 weeks. The observations in this study provide further evidence that TNF-α plays a major role in RA and establishes a method of quantifying the progression of the disease.

Keywords: Rheumatoid arthritis, inflammation, TNF-α, mechanical sensitivity



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