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Nrf2-deficient female mice develop lupus-like autoimmune nephritis
1Institute of Basic Medical Sciences, Institute of Clinical Medicine and Center for TARA, University of Tsukuba, Tsukuba City, Ibaraki, Japan.
Kidney International
|September 29, 2001
Summary
Aged female mice lacking Nrf2 (NF-E2-related factor 2) developed lupus-like autoimmune nephritis, indicating Nrf2 deficiency increases susceptibility to autoimmune diseases. This study investigates the mechanisms behind this nephritis in Nrf2-deficient mice.
Area of Science:
- Immunology
- Nephrology
- Genetics
Background:
- NF-E2-related factor 2 (Nrf2) is crucial for antioxidant and drug metabolism gene induction.
- Nrf2-deficient mice normally develop but aged females show shortened lifespan and severe glomerulonephritis.
Purpose of the Study:
- Investigate the specific glomerulonephritis findings in aged Nrf2-deficient female mice.
- Determine the role of Nrf2 in autoimmune disease susceptibility.
Main Methods:
- Histological and functional analyses of glomerular lesions.
- Measurement of serum immunoglobulins, anti-dsDNA antibody, and lipid peroxidation (TBARS).
Main Results:
- Aged Nrf2-deficient females exhibited severe nephritis with characteristic lesions and immune deposits (IgG, IgM, C3).
- Elevated serum IgG, anti-dsDNA antibody, and TBARS, alongside reduced creatinine clearance and splenomegaly, were observed.
- These findings suggest a lupus-like autoimmune nephritis phenotype.
Conclusions:
- Aged Nrf2-deficient female mice develop lupus-like autoimmune nephritis.
- Nrf2 is a key gene influencing susceptibility to autoimmune diseases.
- Studying this nephritis model can elucidate lupus disease mechanisms.