Lupus, Systemic Lupus Erythematosus (SLE), NZB/W F1 Mouse

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BIOLOGICAL INFORMATION
BACKGROUND INFORMATION
The best characterized mouse model of SLE is NZB/W F1 model. NZBWF1/J hybrids develop lupus-like autoimmunity characterized by immunoglobulin G autoantibody production and progressive severe glomerulonephritis that closely resembles human SLE. The NZBWF1/J mouse model has been used extensively to study the mechanisms of SLE and evaluate the therapeutic efficacy of drug candidates.
ORGANISM
Mouse
ASSAY INFORMATION
ASSAY TYPE
In Vivo
FUNCTIONAL MODE
Antagonist
TESTING INFORMATION
PROCEDURE SUMMARY
Groups of 10 female NZBWF1/J mice at 24-26 weeks of age are used. The urine is screened three times per week for proteinuria. Mice are randomly assigned to different treatment groups each with 10 animals based on the level of proteinuria as well as the body weight after there is kidney damage as evidenced by the presence of proteinuria of ≥30 mg/dl on two occasions two days apart at around 26-28 weeks of age. After kidney damage, vehicle and test articles are administered orally once daily (QD) for 12 weeks. The positive control consists of methylprednisolone (MP) and cyclophosphamide (CTX). MP is given orally at 2 mg/kg once a day for 6 weeks followed by 1 mg/kg once a day for another 6 weeks, and CTX is given orally at 6 mg/kg once a day for 12 weeks. Body weight and proteinuria are recorded once a week, and mortality is observed once daily. Serum blood urea nitrogen (BUN) and creatinine are measured by an automatic analyzer every 4 weeks after dosing. Titers of total IgG and anti-dsDNA antibodies in serum are also detected by ELISA kit every 4 weeks thereafter. The animals are sacrificed at the end of weeks 38 or 40, and kidneys, spleen and draining lymph nodes are collected and weighed.
CRITERIA FOR SIGNIFICANCE
p<0.05 compared to vehicle control is considered significant activity
TURNAROUND TIME
STANDARD
120 Days
CLINICAL RELEVANCE
THERAPEUTIC AREA
Inflammation/Allergy
ADDITIONAL INFORMATION
BRAND
PDS
TESTING LOCATION
Taiwan - Taipei

 

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