Systemic Lupus Erythematosus (SLE) Models

Utilize robust, spontaneous SLE models which more closely represent human disease.

Key Benefits

• Advance SLE agent development with robust in vivo models
• Determine efficacy and response to treatment.
• Select qualified lupus lead agents.

Select preclinical models with diverse mechanisms capturing many key characteristic clinical and pathologic features of SLE including:

• MRL/Faslpr spontaneous model
• NZB/W spontaneous model.

MRL/Faslpr spontaneous model of SLE

• Spontaneous onset starting at 9-10 weeks of age, developing over 7-9 weeks.
• Major phenotype/characteristics:
  • dramatic lymphoproliferation and lymphadenopathy
  • splenomegaly
  • glomerulonephritis (subacute, proliferative) and proteinuria
  • skin lesions
  • expansion of CD3+CD4-CD8- T cells
  • no interferon signature.

NZB/W spontaneous model of SLE

• Spontaneous onset starting around 22-23 weeks of age, developing over 12-13 weeks.
• Major phenotype/characteristics:
  • splenomegaly
  • glomerulonephritis (subacute, proliferative) and proteinuria
  • persistence of long-lived autoreactive plasma cells
  • interferon signature.

Major endpoints for assessment:

• Body weight.
• Skin lesions (in MRL/Faslpr).
• Proteinuria.
• Spleen, kidney, and lymph node size/weight.
• Cytokine levels.
• Blood serum anti-dsDNA antibody levels.
• Blood urea nitrogen (BUN) levels.
• FACS analysis of immune cell populations.
• Kidney histopathology and IHC staining for C3 and IgG levels.