Mouse models of Systemic Lupus Erythematosus (SLE)MODEL DESCRIPTIONSystemic Lupus Erythematosus is a highly complex and heterogenous autoimmune disease more often affecting women in their child-bearing years. The disease is characterized by circulating autoantibodies to nuclear antigens (ANAs) such as anti-Sm and anti-dsDNA, immune complex formation and inflammation in multiple organs. The inflammatory response can lead to tissue damage. Animal models for SLE composes of both induced, spontaneous and genetically modified models. These models, to varying degrees, mimic the hallmarks of the human disease and are good tools for evaluation of efficacy of novel therapies.

CELLULAR IMMUNOLOGYActivated B and T cells promote the development of symptoms characteristic of SLE. Abnormalities with B cell signaling are associated with SLE and also B cells from various lupus-prone mouse strains share the hyperactivation of multiple signaling pathways. In addition, multiple alterations have been found in the T cell receptor signaling cascade of SLE patients. A hallmark of SLE is the interferon (IFN) signature which includes upregulation of type I IFN induced genes by PBMCs that correlates with disease severity. The IFN pathway is also associated with lupus susceptibility. This is best modelled by the pristane induced model in which an eleveated level of type I IFN is seen. The mechanims behind the IFN signature have in part been clarified during the recent years but the exact function of the IFN-regulated genes in the disase process is unclear.

MURINE SLE MODELSThere 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. Among the most studied spontanious 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.

Read more: Systemic Lupus Erythematosus - A Disease with a Dyregulated Type I Ingerfereon System. Hagberg et al. Scand J Immunol. (2015)Animal Models of Molecular Pathology: Systemic Lupus Erythematosus. Sang et al. Prog Mol Biol Transl Sci. (2012)Animal models of interferon signature positive lupus. Zhuang et al. Front Immunol. (2015)

NZB/W F1 MRL/lpr

Strain NZB/W F1 MRL/lpr

Disease induction Spontaneous Spontaneous

PIL Standard

C57Bl.6 or Balb/c

Pristane i.p.

Sugested study lenght 35 weeks 20 weeks 30 weeks

Urine protein From w 30 From w 16 Not detected

PIL ROS defective

Balb/c.Ncf1*/*

Pristane i.p.

20 weeks

From w 15

ANAs anti-dsDNA anti-dsDNA anti-dsDNA anti-dsDNA

Kidney manifistations C3 and Ig deposits Under analysis C3 and Ig deposits Under analysis

Spontaneous Lupus Models in MiceMODEL DESCRIPTIONSystemic Lupus Erythematosus is a highly complex and heterogenous autoimmune disease more often affecting women in their child-bearing years. The disease is characterized by circulating autoantibodies to nuclear antigens (ANAs) such as anti-Sm and anti-dsDNA, immune complex formation and inflammation in multiple organs. The inflammatory response can lead to tissue damage. Animal models for SLE composes of both induced, spontaneous and genetically modified models. These models, to varying degrees, mimic the hallmarks of the human disease and are good tools for evaluation of efficacy of novel therapies.

CHARACTERISTICSAmong the most studied spontanious 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/chormatin autoantibodies. MRL/lpr mice do not develop anti-RNP antibodies. No IFN singature can be found in this model.

MRL/lpr NZB/W

C3 deposits in kidneys (NZB/W) IG deposits in kidneys (NZB/W)

Read more: Systemic Lupus Erythematosus - A Disease with a Dyregulated Type I Ingerfereon System. Hagberg et al. Scand J Immunol. (2015)Animal Models of Molecular Pathology: Systemic Lupus Erythematosus. Sang et al. Prog Mol Biol Transl Sci. (2012)Animal models of interferon signature positive lupus. Zhuang et al. Front Immunol. (2015)

Induced Lupus modelsin miceMODEL DESCRIPTIONSystemic Lupus Erythematosus is a highly complex and heterogenous autoimmune disease more often affecting women in their child-bearing years. The disease is characterized by circulating autoantibodies to nuclear antigens (ANAs) such as anti-Sm and anti-dsDNA, immune complex formation and inflammation in multiple organs. The inflammatory response can lead to tissue damage. Animal models for SLE composes of both induced, spontaneous and genetically modified models. These models, to varying degrees, mimic the hallmarks of the human disease and are thus good tools for evaluation of efficacy of novel therapies.

CHARACTERISTICSPristane (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 characterised 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, involved in production of oxygen radicals, disease develops faster and are more severe than in standard strains.

Read more: Systemic Lupus Erythematosus - A Disease with a Dyregulated Type I Ingerfereon System. Hagberg et al. Scand J Immunol. (2015)Animal Models of Molecular Pathology: Systemic Lupus Erythematosus. Sang et al. Prog Mol Biol Transl Sci. (2012)Animal models of interferon signature positive lupus. Zhuang et al. Front Immunol. (2015)

Balb/CC3 deposits kidneys Control Pristane

Ig Deposits kidneys Control Pristane

C57Bl/6C3 deposits kidneys Control Pristane

Ig Deposits kidneys Control Pristane