mortality/aging
• after lipopolysaccharide (LPS) treatment to induce acute endotoxic shock, mice show typical signs of endotoxic shock but 90% of treated animals survive to 24 hours compared to 37% of wild-type; all wild-type die by 36 hours whereas no more death of null mice is observed after 36 hours
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• mice implanted with B16F1 melanoma tumor cells show reduced survival time after implantation compared to wild-type (<40 days vs >60 days)
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cardiovascular system
N |
• in contrast to wild-type mice after 24 hours after LPS treatment, no muscular degradation or myocytolysis is seen
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• in treated mutants, myocardium is usually preserved, with some animals having mild signs of myofibril disorganization or mitochondrial damage
• most mitochondria do not exhibit shape irregularities, dilation, degeneration of cristae or rupture, compared to those in wild-type myocytes
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• preischemic values of heart rate (HR), coronary flow (CF), aortic flow (AF) and aortic pressure (AOP) are significantly reduced compared to wild-type values
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• incidence of reperfusion-induced ventricular fibrillation is significantly increased (83% vs 33% in wild-type mice)
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• after global ischemia-reperfusion (IR), hearts of Tgm2-null mice show more severe infarct and decreased function compared to wild-type hearts after IR
• after 40 minutes of ischemia followed by 120 minutes of reperfusion, aortic flow is reduced by 3-fold relative to wild-type
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• significantly increased compared to wild-type
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cellular
• relative to wild-type, ATP production is impaired in skeletal and cardiac muscle following prolonged physical effort in mice (IR injury) that depletes ATP stores
(J:126414)
• when complex III is inhibited by antimycin A, addition of ATP (resulting in ATP hydrolysis and proton pumping by complex V) results in significantly slower rate of membrane polarization than in wild-type mitochondria, reflecting defect in ATPase function (in mice with no IR injury)
(J:126414)
• under basal conditions, mitochondrial complex I activity is lower (45% decrease) than in wild-type and complex II activity is significantly increased (by 205%) compared to wild-type
(J:131975)
• after LPS-induced septic shock, complex I and II activities are unaffected but in wild-type mitochondria, activities of both complexes are substantially reduced
(J:131975)
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hematopoietic system
• after LPS treatment, in mutants, there is a 2-fold increase in macrophages infiltrating peritoneal cavity at 24 hours, but in wild-type, infiltrating cells are mixed with neutrophils, mast cells and lymphocytes detected
• 1.5 hours after LPS treatment, serum levels of many cytokines including Il-6, Ifng, and G-CSF are elevated, peaking at 6 hours post-injection; however, while levels remain heightened in wild-type at 24 hours, levels in mutants have returned to steady-state values
• polymorphonuclear neutrophil cell populations are unaffected in contrast to 15-fold increase in neutrophils in peritoneal cavity in wild-type mice at 24 hours
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immune system
N |
• no significant increase in neutrophil infiltration of venules and glomeruli is detected, compared to 4-fold increase in wild-type relative to baseline after LPS treatment
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• after LPS treatment, in mutants, there is a 2-fold increase in macrophages infiltrating peritoneal cavity at 24 hours, but in wild-type, infiltrating cells are mixed with neutrophils, mast cells and lymphocytes detected
• 1.5 hours after LPS treatment, serum levels of many cytokines including Il-6, Ifng, and G-CSF are elevated, peaking at 6 hours post-injection; however, while levels remain heightened in wild-type at 24 hours, levels in mutants have returned to steady-state values
• polymorphonuclear neutrophil cell populations are unaffected in contrast to 15-fold increase in neutrophils in peritoneal cavity in wild-type mice at 24 hours
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renal/urinary system
N |
• 24 hours after LPS treatment, there is no obvious renal damage detected compared to moderate tubular injury observed in wild-type
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neoplasm
• after implantation of B16F1 melanoma tumor cells, tumors show signicantly increased growth (larger size) between 16 and 22 days compared to implanted wild-type
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homeostasis/metabolism
• after global ischemia-reperfusion (IR), hearts of Tgm2-null mice show more severe infarct and decreased function compared to wild-type hearts after IR
• after 40 minutes of ischemia followed by 120 minutes of reperfusion, aortic flow is reduced by 3-fold relative to wild-type
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• significantly increased compared to wild-type
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muscle
• in treated mutants, myocardium is usually preserved, with some animals having mild signs of myofibril disorganization or mitochondrial damage
• most mitochondria do not exhibit shape irregularities, dilation, degeneration of cristae or rupture, compared to those in wild-type myocytes
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