Analysis Tools
mortality/aging
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• mice exhibit a higher mortality rate within the first 100 days of life
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• mice exhibit a higher mortality rate within the first 100 days of life
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• male, but not female, homozygotes are born at sub-Mendelian ratios
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growth/size/body
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• mice are smaller than wild type controls at 3 weeks of age
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• mice exhibit reduced body weight at P28
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immune system
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• bone marrow-derived macrophages (BMDMs) are highly impaired in inflammasome activation and mature IL-1beta secretion
• in response to inflammasome activation, BMDMs undergo extensive reduction in mitochondrial volume and produce reduced levels of reactive oxygen species (ROS) relative to control BMDMs
• upon stimulation of BMDMs with LPS and the NLRP3 inflammasome agonist nigericin, translocation of the inflammasome adaptor protein ASC to the detergent-insoluble compartment and ASC oligomerization are severely blunted, unlike in wild-type BMDMs
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• pretreatment with the antioxidant N-acetyl cysteine (NAC) fails to significantly reduce IL-1beta secretion by bone marrow-derived macrophages (BMDMs) in response to LPS plus nigericin stimulation, unlike in control BMDMs
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• upon stimulation with the NLRP3 inflammasome agonists silica, nigericin, ATP, or the AIM2 inflammasome agonist poly(dA:dT), LPS-primed BMDMs exhibit reduced levels of mature IL-1beta in response to all inflammasome agonists tested relative to control BMDMs
• nigericin-induced IL-1beta secretion by LPS-primed BMDMs is reduced at all time points tested, indicating that reduced IL-1beta secretion is not due to a delayed response
• although LPS-primed BMDMs show normal IL-1beta mRNA expression levels, nigericin-treated BMDMs display reduced levels of cleaved active caspase 1, indicating a defect in pro-IL-1beta processing through caspase 1-associated inflammasome
• upon infection with vesicular stomatosis virus (VSV), LPS-primed BMDMs show reduced IL-1beta release relative to control BMDMs
• upon injection of LPS plus Alum (to induce peritonitis), mice produce significantly lower levels of IL-1beta than wild-type controls
• in contrast to BMDMs, bone marrow-derived dendritic cells (BMDCs) exhibit normal IL-1beta secretion
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cellular
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• primary mouse embryonic fibroblasts (MEFs) treated with TNF, z-VAD-fmk, and the Smac mimetic BV6 exhibit normal levels of necroptosis relative to wild-type MEFs
• BMDMs respond normally to LPS and z-VAD-fmk-induced necroptosis relative to wild-type BMDMs
• LPS-primed BMDMs and BMDCs exhibit normal cell death induced by LPS or LPS plus nigericin relative to similarly treated control cells
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• LPS treatment causes fragmentation of BMDM mitochondria and a concomitant reduction in mitochondrial surface and volume, unlike in control BMDMs
• nigericin treatment of LPS-stimulated BMDMs fails to cause further mitochondria fragmentation, unlike in control BMDMs
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• mitochondria of untreated bone marrow-derived macrophages (BMDMs) appear elongated with increased volume and surface
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• untreated or LPS-treated BMDMs exhibit lower basal ROS production than control BMDMs
• although LPS plus nigericin-treated BMDMs show a transient increase in ROS production at 15 min post-stimulation, ROS levels are lower than in control BMDMs by 30 min post-stimulation
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hematopoietic system
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• bone marrow-derived macrophages (BMDMs) are highly impaired in inflammasome activation and mature IL-1beta secretion
• in response to inflammasome activation, BMDMs undergo extensive reduction in mitochondrial volume and produce reduced levels of reactive oxygen species (ROS) relative to control BMDMs
• upon stimulation of BMDMs with LPS and the NLRP3 inflammasome agonist nigericin, translocation of the inflammasome adaptor protein ASC to the detergent-insoluble compartment and ASC oligomerization are severely blunted, unlike in wild-type BMDMs
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