Disease Pathophysiology

• MS is a CNS inflammatory disease caused by an autoimmune response against the myelin sheath insulation of nerve fibers, results in loss of motor-neuron control.

• In mice, MOG peptide induces an auto-immune response, resulting in demyelination of nerve cells. Hindlimb and forelimb paralysis ensues and is scored/quantified.

Disease Induction

• SC injection of 0.2mg MOG_35-55 (myelin oligodendrocyte glycoprotein 35-55) in 0.4mg killed mycobacterium tuberculosis H37Ra, 0.1ml at 2 sites on the back at time= 0 hours.

• IP injection of 600ng pertussis toxin at time= 2 hours and again at time= 22-26 hours

PD/Endpoint Analysis

• Hindlimb/forelimb scoring of paralysis, scale 0-5

• CD20, IL-17, GM-CSF analysis

Disease Pathophysiology

• CIA model driven by adaptive immune responses, includes presence of rheumatoid factor or anticitrullinated peptide antibody

• Adjuvant induced models rely on innate and T-cell responses

• Recombinant human Glucose-6-phosphate isomerase (rh-GPI) induces T-cell dependent inflammatory arthritis in genetically susceptible mice (male DBA/1)

• Th2-driven model, sustained T-cell help to B cells leads to the production of high-affinity IgG1 antibodies against G6PI, arthritogenic

Disease Induction

• Animals are injected SC at the base of the tail (2 sites of injection, 100µl/site), using a 27g needle with 400µg of rhGPI or collagen that has been emulsified 1:1 with CFA

PD/Endpoint Analysis

• Scoring of footpad swelling: from 0 = normal, 1 = erythema and slight swelling of the major joint, 2 = moderate to severe swelling of the major joint, 3 = severe swelling of the entire paw.

• IL-17, IL-1β, TNF, CD20 analysis

• ob/ob leptin deficient mouse and db/db mouse model for diabetic dyslipidemia

• Oral Glucose Tolerance Test