Nephrotoxic Nephritis Models
Nephritis is an immune complex-mediated autoimmune disease characteriszd by inflammation of the kidneys that develops through a mechanism that is not completely understood. Nephritis is clinically diagnosed through urine tests, blood tests, and kidney biopsies. Charles River has developed a translational nephritis mouse model induced by nephrotoxic antiserum (NTS), preceded by administration of sheep immunoglobulin (IgG) in complete freund’s adjuvant (CFA).
Readouts of the nephritis mouse model include in-life blood creatinine, proteinuria, pharmacokinetic and/or pharmacodynamic (PK/PD) blood collections and blood urea nitrogen (BUN) readings.
Nephritis Mouse Model Study Endpoints Include:
- PK/PD blood collections
- Blood creatinine analysis
- Clinical observations
- Histopathological evaluation
Figure 1: Flow cytometry of kidney immune infiltrate in NTS nephritis model is shown. NTS nephritis mouse models are characterized by an influx of CD4+ T cells in kidneys. Treatment with rapamycin reduces the levels of CD4+ T cells. Data is presented as a percentage of viable, single, and CD45+ cells.
Figures 2 & 3: Normal kidney – Uniform small glomeruli and uniform tubules
Figures 4 & 5: NTS model kidney – Tubular dilation and protein accumulation, interstitial inflammation, and glomerulosclerosis
Figure 6: Sera from mice with NTS nephritis were tested for mouse anti-sheep IgG in an end-point titre ELISA. Rapamycin administration causes a decrease in serum total IgG and serum IgG1, IgG2b, and IgG2c subclasses. Levels pre-disease induction were negligible.
Frequently Asked Questions (FAQs) for Nephritis Mouse Models:
Which lupus nephritis model should I use?
Nephritis is a common complication of autoimmune disease such as Systemic Lupus Erythematosus (SLE), and Charles River has a SLE animal model which can model the nephritis and systemic disease associated with SLE. Multiple mouse models have been developed to investigate the pathogenesis associated with the autoimmune reaction seen in SLE, each with strengths and limitations, making the choice of the appropriate model challenging. Our team of expert immunologists can aid you in this choice and run the relevant model for you with extensive ex vivo analysis to ensure the immune response is appropriately characterized.
What animal models are available for nephritis?
In addition to spontaneous models of Lupus nephritis such as Charles River’s NZB/W mouse model, there are also induced models such as our Nephrotoxic Anti-Serum Nephritis mouse model. To ensure easy translation of client compounds into the clinic, all Charles River’s models are characterized by the immune-complex formation and chemokine/cytokine response associated with Nephritis.