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

AbstractCaspase (CASP) 3 is known as a representative effector CASP of apoptosis and recently as a mediator in inflammatory cell death called pyroptosis. Interestingly, homozygotes ofCasp3 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 ofCasp3 KO mice with B6-background that survived for 8 –12 months showed abnormality in the kidney and spleen but not in other organs. Briefly, theseCasp3 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 inflammatoryCasps, includingCasp12, was observed in theseCasp3 KO kidneys. Moreover, theseCasp3 KO mice showed mild splenomegaly compared with WT mice. Thus, the long-survivingCasp3 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.
Source: Cell and Tissue Research - Category: Cytology Source Type: research