Inducing Arthritis In C57Bl/6 Strains with High Rates of Incidence in a Rapid 12-Day Model

Abstract

BioTechniquesVol. 50, No. 3 Sponsored Paper - Application ForumOpen AccessInducing arthritis in C57Bl/6 strains with high rates of incidence in a rapid 12-day modelThe collagen antibody-induced arthritis model using only 2 mg/mouse ArthritoMab™ Antibody CocktailMD BiosciencesMD Biosciences2575 University Avenue, W #100, St Paul, MN 55114, USASearch for more papers by this authorPublished Online:28 Jun 2018https://doi.org/10.2144/000113630AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinkedInRedditEmail IntroductionC57Bl/6 is a common background for generating genetically modified strains for use in in vivo models of arthritis. While these strains are commonly used, they are also known for requiring larger amounts of induction reagents, present with lower incidence rates and often times a milder disease course. In the classical CIA model, investigators are often required to nearly double the group size to accommodate the incidence rates, which can be as low as 50%. In the alternative collagen antibody–induced arthritis (CAIA) model, investigators often need to boost levels of antibody substantially. MD Biosciences arthritogenic cocktail of four antibodies has been optimized for use in C57Bl/6 strains allowing investigators to induce arthritis with nearly 100% incidence using as low as 2 mg/mouse. The cocktail consists of four monoclonal antibodies to CII that bind to the well-defined epitopes C1, J1, D3, and U1.Method and resultsMale C57Bl/6 animals (6–8 weeks of age) were administered 2, 4, and 8 mg of ArthritoMab™ Cocktail (IV) on day 0 followed by 100 µg LPS (IP) on day 3. Administration of the antibody cocktail produces inflammation involving both rear and front paws in >95% of the animals. Animals are scored on a scale of 0–4 for each paw giving a maximum total score of 16. Dexamethasone is administered daily (1 mg/kg IP) as a positive control in order to demonstrate that an effective test item can reduce inflammation. The data shows that 2, 4, and 8 mg/mouse all give a similar disease course in vehicle-treated animals. Data also shows that reducing the amount of cocktail by up to 50% only reduces disease scores by 25%, allowing investigators to reduce the amount of antibody according to the disease severity required for their purposes (Figure 1).Figure 1. Total clinical score in C57Bl/6 using 2 mg, 4 mg, and 8 mg ArthritoMab™ Antibody Cocktail.Difference in disease score between 2 mg and 8 mg is ∼25%.Figure 2. Histology showing pannus formation, hyperplasia, erosion, and infiltration in arthritic C57Bl/6 using 2 mg ArthritoMab™ Antibody Cocktail.Optimizing the model for each laboratoryEach laboratory will need to optimize the appropriate protocol for their laboratory, since strains, housing conditions, animal suppliers, feed, and environmental factors will contribute to severity of disease. It is recommended that investigators do a small titration study to find the optimum amount of antibody and LPS for their conditions. Investigators can determine how severe they require the disease to be, as well as extend the model from 12 days to 18 days to include a 6-day recovery phase.FiguresReferencesRelatedDetails Vol. 50, No. 3 Follow us on social media for the latest updates Metrics Downloaded 285 times History Published online 28 June 2018 Published in print March 2011 Information© 2011 Future Science LtdPDF download