Analysis Tools
growth/size/body
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• most mice are smaller and thinner at weaning
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behavior/neurological
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• about 30% of mice exhibit severe neurological abnormalities, including hindlimb paralysis and circular movement
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• hindlimb paralysis is one of the phenotypes seen in mice with neurological abnormalities
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• circling is one of the phenotypes seen in mice with neurological abnormalities
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cardiovascular system
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• blood vessel occlusion in the eyes of 70% mice at 5-10 weeks of age
• central and branch retinal artery occlusions
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• dropout of retinal vasculature and perivascular leakage
• central and branch retinal artery occlusions
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• hyalinosis in interlobular arteries and arterioles
• all mice contain atypical hemolytic uremic syndrome-like pathological changes in the kidney
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• kidney shows narrowing of the capillary lumen in glomeruli
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• kidney shows capillary microthrombi with endothelial swelling in glomeruli
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• mice with neurological abnormalities show the presence of thrombi and/or intracerebral hemorrhage in the brain
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muscle
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• endothelium-dependent and independent relaxations of small mesenteric arteries (i.e. smooth muscle cells) are impaired
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hematopoietic system
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• low blood hemoglobin levels
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• severe thrombocytopenia at 4 and 8 weeks of age
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homeostasis/metabolism
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• creatine levels are higher but are highly variable
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• increase in plasma ADAMTS13 activity
• increase in plasma VWF antigen levels and lower ratio of high- to low- molecular weight VWF multimers
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• BUN levels progressively increase with age
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• mice exhibit a reduction in plasma complement levels, with lower levels of intact C3, factor B, and C5
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• mice develop systemic thrombophilia involving large blood vessels in multiple organs, including liver, lung, spleen and kidney
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• thrombi in medium and large blood vessels in all organs examined, including liver, lung, spleen, and kidney, with most thrombi in veins and pulmonary arteries
• no thrombus formation is seen in fetal organs but some is seen in 1 week old mice
• mice with symptoms of stroke are more likely to have multiorgan thrombosis, but portal vein thrombosis is more common and less correlated with stroke symptoms
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• mice with neurological abnormalities show the presence of thrombi in the brain
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• thrombosis in interlobular arteries and arterioles of the kidney
• glomeruli exhibit microthrombi and large vein thrombi
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• kidney shows capillary microthrombi in glomeruli
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• thrombi in pulmonary arteries
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• portal vein thrombosis is present in the liver of more than 80% of mice
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• lower levels of C5 in plasma
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• about 30% of mice show symptoms of stroke and ischemic retinopathy
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immune system
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• mice exhibit a reduction in plasma complement levels, with lower levels of intact C3, factor B, and C5
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• lower levels of C5 in plasma
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• plasma AP complement activity is lower
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mortality/aging
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• 48% of mice die by 30 weeks of age
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nervous system
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• mice with neurological abnormalities show the presence of thrombi and/or intracerebral hemorrhage in the brain
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• mice with neurological abnormalities exhibit ischemic brain injury
• ischemic brain injury is only seen in mice with symptoms of stroke
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renal/urinary system
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• thrombotic microangiopathy-like renal pathology is seen in all mice regardless of neurological phenotype
• kidney shows double contours of glomerular basement membrane with capillary microthrombi and endothelial swelling with narrowing of the capillary lumen in glomeruli
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• hyalinosis in interlobular arteries and arterioles
• all mice contain atypical hemolytic uremic syndrome-like pathological changes in the kidney
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• 68% of the glomeruli show microthrombi
• 52% of the glomeruli show large vein thrombi
• 78% of the glomeruli show arteriolar hyalinosis
• glomerular deposition of C3 and fibrin indicating complement activation and vascular injury
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• kidney shows narrowing of the capillary lumen in glomeruli
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• kidney shows capillary microthrombi with endothelial swelling in glomeruli
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• mesangial expansion in the kidney
• mesangial expansion in glomeruli is already seen in 1 week old mice but not at E15
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• 53% of the glomeruli show expanded matrix
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vision/eye
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• about 30% of mice show symptoms of stroke and ischemic retinopathy
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white pupil
(
J:240426
)
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• in some mice
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• ischemic injury is seen in the retina, including retinal edema, whitening, and cotton wool spots in most mice
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• dropout of retinal vasculature and perivascular leakage
• central and branch retinal artery occlusions
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• about 9% of mice have retinal detachments, most likely resulting from exudation secondary to infarctions in the choroidal vasculature
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| atypical hemolytic-uremic syndrome | DOID:0080301 | J:240426 | ||
