Lupus Efficacy Studies

Let In Vivo Pharmacology Services at JAX perform your lupus-related efficacy study using robust systemic lupus erythematosus (SLE) mouse models.

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Model Comparison

Phenotype NZBWF1/J MRL-Lpr
Proteinuria
Autoantibodies
Lymphadenopathy
Splenomegaly +/-
Glomerulonephritis
Dermatitis/Psoriasis x
SLE Genes x
Gender Bias ✓ (F) ✓ (F)
50% Survival Age ~45 Weeks ~25 Weeks
Age of Onset ~30 Weeks ~10-12 Weeks
Available Age Range 4 to 20 Weeks 4 to 8 Weeks

Example Efficacy Study Using MRL-lpr

•  8 week old female MRL-lpr mice (10 mice per group)
•  Disease onset assessed by proteinuria levels
•  Prophylatic (prior to detection of proteinuria) or therapeutic (after detection of proteinuria) dosing
•  Proteinuria measured throughout the study
•  Spleen and kidneys collected and weighed at study terminus; kidneys processed for histology
•  Anti-dsDNA and total IgG can be assessed by ELISA

Experimental Timelines

 

Representative Data

(error bars = SEM)

 

Figure 1. Proteinuria Analysis. Proteinuria begins to increase by 13 weeks of age. Treatment with cyclophosphamide beginning at 8 weeks inhibits the increase in proteinuria in MRL-lpr mice.

 

Figure 2: Survival. Cyclophosphamide improves survival in MRL-lpr mice.

 

Figure 3. Anti-dsDNA Antibody Concentration in Sera. Serum anti-dsDNA antibody levels can be reduced with cyclophosphamide treatment in MRL-lpr mice. *p<0.05

 

Figure 4: Kidney Pathology Analysis. Histopathology scoring of different regions of the kidney shows improvements following cyclophosphamide treatment in MRL-lpr mice. *p< 0.05, **p< 0.01

Example Efficacy Study Using NZBWF1

  • - Female NZBWF1/J mice (10 mice per group)
  • Disease onset assessed by proteinuria levels
  • Prophylactic (prior to detection of proteinuria) or therapeutic (after detection of proteinuria) dosing
  • Spleen and kidneys collected and weighed at study terminus, kidneys processed for histology
  • Anti-dsDNA and total IgG can be assessed by ELISA
  • Immunophenotyping of splenocytes

Experimental Timelines

 

Representative Data

(error bars = SEM)

 

Figure 1: Proteinuria Analysis. Proteinuria begins to increase by 27 weeks of age. Treatment with cyclophosphamide beginning at 26 weeks of age inhibits elevations in proteinuria in NZBWF1/J mice.

 

Figure 2: Survival Cyclophosphamide improves survival in NZBWF1 mice.

Figure 3. Anti-dsDNA Antibody Concentration in Sera: Serum anti-dsDNA antibody levels can be reduced with cyclophosphamide treatment in NZBWF1 mice. ****p<0.0001

Figure 4. Kidney Pathology Analysis: Histopathology scoring of different regions of the kidney shows improvements following cyclophosphamide treatment in NZBF1/J mice. **p< 0.01, ****p<0.0001

Figure 5:  Immunophenotyping Immune cell profiling of splenocytes from NZBWF1/J mice at 36 weeks of age following prophylactic treatment with cyclophosphamide. Reduced effector memory T cells and B cells translates into reduced clinical signs of disease. **p< 0.01, ***p<0.001, ****p<0.0001K/em>