Phenotypes Associated with This Genotype

Genotype
MGI:6314805

• Allelic Composition: Cfh^tm1.1Song/Cfh^tm1.1Song
• Genetic Background: involves: C57BL/6

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

growth/size/body

decreased body size ( J:240426 )

• most mice are smaller and thinner at weaning

behavior/neurological

abnormal behavior ( J:240426 )

• about 30% of mice exhibit severe neurological abnormalities, including hindlimb paralysis and circular movement

hindlimb paralysis ( J:240426 )

• hindlimb paralysis is one of the phenotypes seen in mice with neurological abnormalities

circling ( J:240426 )

• circling is one of the phenotypes seen in mice with neurological abnormalities

cardiovascular system

artery occlusion ( J:240426 )

• blood vessel occlusion in the eyes of 70% mice at 5-10 weeks of age

• central and branch retinal artery occlusions

abnormal retina vasculature morphology ( J:240426 )

• dropout of retinal vasculature and perivascular leakage

• central and branch retinal artery occlusions

abnormal kidney vasculature morphology ( J:240426 )

• hyalinosis in interlobular arteries and arterioles

• all mice contain atypical hemolytic uremic syndrome-like pathological changes in the kidney

abnormal glomerular capillary morphology ( J:240426 )

• kidney shows narrowing of the capillary lumen in glomeruli

abnormal glomerular capillary endothelium morphology ( J:240426 )

• kidney shows capillary microthrombi with endothelial swelling in glomeruli

intracerebral hemorrhage ( J:240426 )

• mice with neurological abnormalities show the presence of thrombi and/or intracerebral hemorrhage in the brain

muscle

impaired muscle relaxation ( J:240426 )

• endothelium-dependent and independent relaxations of small mesenteric arteries (i.e. smooth muscle cells) are impaired

hematopoietic system

anemia ( J:240426 )

• anemia at 4 and 8 weeks of age

• however, white blood cell count is normal

decreased hemoglobin content ( J:240426 )

• low blood hemoglobin levels

thrombocytopenia ( J:240426 )

• severe thrombocytopenia at 4 and 8 weeks of age

reticulocytosis ( J:240426 )

homeostasis/metabolism

increased creatine level ( J:240426 )

• creatine levels are higher but are highly variable

abnormal blood homeostasis ( J:240426 )

• increase in plasma ADAMTS13 activity

• increase in plasma VWF antigen levels and lower ratio of high- to low- molecular weight VWF multimers

increased blood urea nitrogen level ( J:240426 )

• BUN levels progressively increase with age

decreased circulating complement protein level ( J:240426 )

• mice exhibit a reduction in plasma complement levels, with lower levels of intact C3, factor B, and C5

abnormal blood coagulation ( J:240426 )

• mice develop systemic thrombophilia involving large blood vessels in multiple organs, including liver, lung, spleen and kidney

abnormal thrombosis ( J:240426 )

• 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

abnormal brain thrombosis ( J:240426 )

• mice with neurological abnormalities show the presence of thrombi in the brain

abnormal kidney thrombosis ( J:240426 )

• thrombosis in interlobular arteries and arterioles of the kidney

• glomeruli exhibit microthrombi and large vein thrombi

abnormal glomerular capillary thrombosis ( J:240426 )

• kidney shows capillary microthrombi in glomeruli

abnormal kidney venous thrombosis ( J:240426 )

abnormal lung thrombosis ( J:240426 )

• thrombi in pulmonary arteries

abnormal hepatic portal vein thrombosis ( J:240426 )

• portal vein thrombosis is present in the liver of more than 80% of mice

decreased complement C5 level ( J:240426 )

• lower levels of C5 in plasma

increased susceptilbility to retina ischemic injury ( J:240426 )

• about 30% of mice show symptoms of stroke and ischemic retinopathy

immune system

decreased circulating complement protein level ( J:240426 )

• mice exhibit a reduction in plasma complement levels, with lower levels of intact C3, factor B, and C5

decreased complement C5 level ( J:240426 )

• lower levels of C5 in plasma

decreased serum complement activity ( J:240426 )

• plasma AP complement activity is lower

mortality/aging

premature death ( J:240426 )

• 48% of mice die by 30 weeks of age

nervous system

intracerebral hemorrhage ( J:240426 )

• mice with neurological abnormalities show the presence of thrombi and/or intracerebral hemorrhage in the brain

brain ischemia ( J:240426 )

• mice with neurological abnormalities exhibit ischemic brain injury

• ischemic brain injury is only seen in mice with symptoms of stroke

renal/urinary system

abnormal kidney morphology ( J:240426 )

• kidney shows double contours of glomerular basement membrane with capillary microthrombi and endothelial swelling with narrowing of the capillary lumen in glomeruli

• thrombotic microangiopathy-like renal pathology is seen in all mice regardless of neurological phenotype

abnormal kidney vasculature morphology ( J:240426 )

• hyalinosis in interlobular arteries and arterioles

• all mice contain atypical hemolytic uremic syndrome-like pathological changes in the kidney

abnormal renal glomerulus morphology ( J:240426 )

• 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

abnormal glomerular capillary morphology ( J:240426 )

• kidney shows narrowing of the capillary lumen in glomeruli

abnormal glomerular capillary endothelium morphology ( J:240426 )

• kidney shows capillary microthrombi with endothelial swelling in glomeruli

abnormal glomerular mesangium morphology ( J:240426 )

• mesangial expansion in the kidney

• mesangial expansion in glomeruli is already seen in 1 week old mice but not at E15

expanded mesangial matrix ( J:240426 )

• 53% of the glomeruli show expanded matrix

vision/eye

increased susceptilbility to retina ischemic injury ( J:240426 )

• about 30% of mice show symptoms of stroke and ischemic retinopathy

white pupil ( J:240426 )

• in some mice

abnormal retina morphology ( J:240426 )

• ischemic injury is seen in the retina, including retinal edema, whitening, and cotton wool spots in most mice

abnormal retina vasculature morphology ( J:240426 )

• dropout of retinal vasculature and perivascular leakage

• central and branch retinal artery occlusions

retina detachment ( J:240426 )

• about 9% of mice have retinal detachments, most likely resulting from exudation secondary to infarctions in the choroidal vasculature

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
atypical hemolytic-uremic syndrome		DOID:0080301		J:240426