Models of Systemic Lupus Erythematosus (SLE)
There are several mouse models for SLE, mimicing different aspects of the disease to varying extent and partial lupus-like syndromes may provide important insights into the pathogenesis of the individual manifestations of SLE. These models, to varying degrees, mimic the hallmarks of the human disease and are good tools for evaluation of efficacy of novel therapies.
Among the most studied spontaneous model strains are the NZB/W F1 and MRL/Lpr strains. The spontaneous models have the advantage that genetic susceptibility factors are important as in human SLE while the pristane induced models have the IFN type I signature.
Spontaneous SLE Models
Among the most studied spontaneous model strains are the NZB/W F1 and MRL/Lpr strains. The NZB/W mice develop severe glumeronephritis and anti-dsDNA antibodies without other clinical or serological manifestations of lupus. Anti-Sm/RNP antibodies are absent. A week IFN signature can be found at later stages of disease.
MRL/lpr mice develop disease with anti-Sm and anti-DsDNA/chromatin autoantibodies. MRL/lpr mice do not develop anti-RNP antibodies. No IFN signature can be found in this model.
Induced SLE models
Pristane (2,6,10,14-tetramethylpentadecane) is an alkane found in plants, shark liver and mineral oil. Pristane can be used to induce autoimmune arthritis in susceptible rat strains. When injected intraperitoneally in non-autoimmune prone mice (B6 or Balb/c) a lupus-like disease develops. Disease is characterized with high levels of anti-dsDNA, anti-Sm/RNP and other lupus related autoantibodies with onset after around 3 months after induction. There is variability in clinical signs between strains and can include glomeronephritis, arthritis, anemia and alevolar hemorrage. As for SLE patients, disease is more severe in females than in males. Pristane induced Lupus show a strong IFN signature. A population of inflammatory monocytes is responsible for most of the IFN production in pristane induced mice but also peripheral dendritic cells play a role. In mice deficient for the Ncf1 protein, which is involved in production of oxygen radicals, disease develops faster and is more severe than in standard strains.