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Immune-associated renal disease found in caspase 3-deficient mice

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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.

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Acknowledgments

The research described in this manuscript was chosen for the Encouragement Award (undergraduate section) at the 161th Japanese Association of Veterinary Anatomists in Ibaraki (11–13 September 2018, Mr. Suzuki).

Funding

This work was supported by the research grant from KAC Co., Ltd (Dr. Ichii).

Author information

T.S. and O.I. designed, performed experiments, and analyzed data. T.N. analyzed data. T.H., Y.H.A.E., and Y.K. designed and reviewed the experiments. All authors were involved in writing the manuscript and provided final approval to publish the manuscript.

Correspondence to Osamu Ichii.

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The authors have no conflicts of interest directly relevant to the content of this article.

Ethical approval

Animal experimentation was approved by the Institutional Animal Care and Use Committee of the Graduate School of Veterinary Medicine, Hokkaido University (approval No. 15-0079, 16-0124). Experimental animals were handled in accordance with the Guide for the Care and Use of Laboratory Animals, Graduate School of Veterinary Medicine, Hokkaido University (approved by the Association for Assessment and Accreditation of Laboratory Animal Care International).

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Cite this article

Suzuki, T., Ichii, O., Nakamura, T. et al. Immune-associated renal disease found in caspase 3-deficient mice. Cell Tissue Res 379, 323–335 (2020) doi:10.1007/s00441-019-03084-w

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Keywords

  • Kidney
  • Glomerulus
  • Caspase 3
  • Knockout
  • Immunity