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Updated: Jan 20, 2026
Evaluation of Caspase Activation to Assess Innate Immune Cell Death
Published on: January 20, 2023
Immune-associated renal disease found in caspase 3-deficient mice
Takashi Suzuki1, Osamu Ichii2, Teppei Nakamura1,3
1Laboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo, 060-0818, Japan.
Abstract:
Caspase (CASP) 3 is known as a representative effector CASP of apoptosis and recently as a mediator in inflammatory cell death called pyroptosis. Interestingly, homozygotes of Casp3 knockout (KO) mice with 129-background show complete embryonic lethality; however, some of those with C57BL/6 (B6)-background (B6.129S1-Casp3tm1Flv/J) survived at a lower rate (KO, 11%; WT, 22%), developing immune abnormality-associated renal phenotypes. Homozygotes of Casp3 KO mice with B6-background that survived for 8-12 months showed abnormality in the kidney and spleen but not in other organs. Briefly, these Casp3 KO kidneys showed proliferative glomerular lesions characterized by increased cells, matrices, immune complex depositions containing IgA and complement 3 in the mesangial area, podocyte injuries and inflammatory cell infiltrations in the tubulointerstitium. However, severe membranous lesion or renal dysfunction was not observed. Increased expression of inflammation-associated gene sets and inflammatory Casps, including Casp12, was observed in these Casp3 KO kidneys. Moreover, these Casp3 KO mice showed mild splenomegaly compared with WT mice. Thus, the long-surviving Casp3 KO mice with B6-background developed renal lesions with altered immune conditions. CASP3 deficiency and aging factors could affect this phenotype by altering the function and/or development of each cell in the kidney and immune organs.
Insights
Caspase 3 knockout mice on a C57BL/6 background showed kidney and spleen abnormalities, including glomerular lesions and splenomegaly, suggesting CASP3 deficiency impacts immune and renal health with aging.
Area of Science:
- Immunology
- Cell Biology
- Renal Pathology
Background:
- Caspase (CASP) 3 is a key effector caspase in apoptosis and pyroptosis.
- Complete Caspase 3 knockout (KO) in mice typically causes embryonic lethality, but some C57BL/6 background mice survive with immune abnormalities.
Purpose of the Study:
- To investigate the long-term effects of Caspase 3 deficiency on renal and immune phenotypes in surviving mice.
- To characterize the specific pathological changes in kidneys and spleens of Caspase 3 KO mice.
Main Methods:
- Generation and characterization of Caspase 3 knockout mice on a C57BL/6 background.
- Histopathological examination of kidneys and spleens from surviving KO and wild-type (WT) mice.
- Analysis of gene expression related to inflammation in kidney tissues.
Main Results:
- Surviving Caspase 3 KO mice (8-12 months old) exhibited kidney abnormalities, including proliferative glomerular lesions, IgA and C3 deposition, podocyte injury, and tubulointerstitial inflammation.
- Mild splenomegaly was observed in KO mice compared to WT.
- Increased expression of inflammation-associated genes and inflammatory caspases (e.g., Caspase 12) was detected in KO kidneys.
Conclusions:
- Long-term survival of Caspase 3 KO mice on a B6 background leads to distinct renal lesions and altered immune conditions.
- Both Caspase 3 deficiency and aging likely contribute to the observed kidney and spleen phenotypes by affecting cellular function and development.
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