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Calorie restriction delays the crescentic glomerulonephritis of SCG/Kj mice
Cherry1, R W Engelman, B Y Wang
1Department of Pediatrics, All Children's Hospital, University of South Florida, St. Petersburg 33701, USA.
Abstract:
Reduced dietary calories can delay the onset and diminish the severity of murine autoimmunities of numerous inbred and hybrid mutant strains. We sought to determine whether the precipitous, autoimmune, crescentic glomerulonephritis of recombinant inbred SCG/Kj mice could be abrogated similarly by calorie restriction. Weanling SCG/Kj mice develop hematuria and proteinuria, and 50% die as 16-week-old young adults. In this study, 113 4-week-old SCG/Kj mice were fed either ad libitum a milled chow (Group A, n = 50), or a semipurified diet (Group B, n = 29), or were fed a calorie-restricted semipurified diet (Group C, n = 34), so that mice of Group C consumed approximately 32% fewer calories, but similar amounts of essential dietary constituents as those of Group B. Calorie restriction of Group C provided modest (P = 0.05) or substantial survival advantage (P = 0.001) compared to the ad libitum feeding of Groups B or A, respectively. Progression to severe glomerular pathology was delayed among Group C mice, with more than a 5-week delay to heavy proteinuria (>100 mg/dl), a >4-week delay to hematuria, and a >5-week delay to median mortality, representing a 20% or 25% extension of median life span, compared to ad libitum-fed Group B and A mice, respectively. Mean glomerular histopathology scores were also lower in calorie-restricted mice compared to the ad libitum-fed cohorts (P = 0.001). Titers of anti-ss-DNA, ds-DNA, and ANCA autoantibodies developed in weanlings prior to the full imposition of calorie restriction and were not reduced significantly by calorie restriction.
Insights
Calorie restriction extended lifespan and delayed kidney disease in SCG/Kj mice. This dietary intervention improved survival and reduced glomerular pathology, but did not affect autoantibody levels.
Area of Science:
- Immunology
- Nephrology
- Nutritional Science
Background:
- Calorie restriction (CR) is known to delay autoimmune diseases in various mouse models.
- SCG/Kj mice spontaneously develop autoimmune crescentic glomerulonephritis, characterized by hematuria and proteinuria, with high mortality in young adulthood.
Purpose of the Study:
- To investigate the efficacy of calorie restriction in abrogating or delaying autoimmune crescentic glomerulonephritis in SCG/Kj mice.
- To assess the impact of CR on survival, disease progression, and autoantibody production in this specific mouse model.
Main Methods:
- 113 weanling SCG/Kj mice were divided into three groups: ad libitum chow (Group A), ad libitum semipurified diet (Group B), and calorie-restricted semipurified diet (Group C, ~32% fewer calories than Group B).
- Mice were monitored for survival, onset of hematuria and proteinuria, progression of glomerular pathology, and titers of anti-ss-DNA, ds-DNA, and ANCA autoantibodies.
Main Results:
- Calorie restriction significantly improved survival rates (P = 0.001 vs. Group A; P = 0.05 vs. Group B), extending median lifespan by 20-25%.
- CR delayed the onset of heavy proteinuria (>100 mg/dl) by over 5 weeks and hematuria by over 4 weeks.
- Mean glomerular histopathology scores were significantly lower in the CR group (P = 0.001), indicating reduced kidney damage.
- Autoantibody titers (anti-ss-DNA, ds-DNA, ANCA) were already elevated before CR initiation and were not significantly affected by the dietary intervention.
Conclusions:
- Calorie restriction effectively delays the onset and progression of autoimmune crescentic glomerulonephritis in SCG/Kj mice, leading to significant survival benefits.
- While CR mitigates kidney pathology and extends lifespan, it does not appear to reduce pre-existing autoantibody production in this model.
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