Preclinical Lupus Models and 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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Example Efficacy Study Using MRL-lpr

•  8 week old female MRL-lpr mice
•  Disease onset assessed by proteinuria levels
•  Prophylatic (prior to detection of proteinuria) or therapeutic (after detection of proteinuria) dosing
•  Blood urea nitrogen (BUN) measured throughout 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

lupus studies

Representative Data

(error bars = SEM)

Lupus Studies

Figure 1: Blood urea nitrogen (BUN) increases in MRL-lpr can
be prevented by cyclophosphamide treatment.

lupus studies

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

lupus studies

Figure 3: Proteinuria increases around 10 weeks of age. CellCept (mycophenolate mofetil) can reduce the proteinuria increase.

lupus studies

Figure 4: Histopathology scoring of different regions of the kidney shows improvements following cyclophosphamide treatment.

 
Conclusions

• MRL-lpr mice spontaneously develop symptoms that resemble human SLE, including organ
  malfunction (proteinuria, elevated BUN, organ weight gain, and kidney histopathology) and mortality.

• Cyclophosphamide and CellCept, both human therapeutics, showed efficacy in this mouse model.

Example Efficacy Study Using NZBWF1

• Female NZBWF1/J mice (10 mice per arm)
• Weekly proteinuria scoring initiated at 25 weeks of age
• Dosing initiated at 26 weeks of age
• Body weights measured twice weekly
• Organ weights (kidneys, spleen, lymph nodes) collected at study terminus
• Blood collections and serum chemistry (BUN and creatinine) throughout study
• Anti-dsDNA and total IgG can be assessed by ELISA

Experimental Timelines

lupus studies

Representative Data

(error bars = SEM)

Lupus Studies

Figure 1: Changes in proteinuria as a measure of Disease Activity Indexing (DAI). Treated mice showed marked reduction in
proteinuria by 5 weeks on study.

lupus studies

Figure 2: Treated mice on study maintained 100% survival compared to 80% survival at 60 days for vehicle treated controls.

lupus studies

Figure 3: Serum creatinine was reduced in treated mice, particularly at 11 weeks of treatment, indicating improved
kidney function.

lupus studies

Figure 4: Serum Blood Urea Nitrogen (BUN) was reduced in treated mice at all time points measured, demonstrating improved kidney function.