Phenotypes Associated with This Genotype

Genotype
MGI:3696558

• Allelic Composition: Serpinc1^tm1Dwr/Serpinc1^tm1Dwr
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

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

cellular

hepatic necrosis ( J:115658 )

• coagulative necrosis in the liver

mortality/aging

premature death ( J:115658 )

• beyond weaning, survival remains compromised with death at various ages and only about 30% survival beyond 6 months

neonatal lethality, incomplete penetrance ( J:115658 )

• frequently die within 24 hours after birth

postnatal lethality, incomplete penetrance ( J:115658 )

• only 60% reach weaning age

homeostasis/metabolism

abnormal blood coagulation ( J:115658 )

• plasma displays low heparin cofactor activity

abnormal thrombosis ( J:115658 )

• develop spontaneous life-threatening thrombosis, as early as the day of birth; rarely seen at E18.5

• thormbotic events in adults are most prominent in the heart, liver, and in ocular, placental, and penile vessels

• pentasaccharide does not inhibit thrombus formation as in wild-type when thrombosis is induced

• thrombosis is not seen in other organs nor in the larger vessels like the caval vein, femoral artery and vein, and branchial vein

abnormal cardiac thrombosis ( J:115658 )

• 6 of 16 adults show massive thrombosis in the atria and/or ventricles, often associated with leukocyte infiltration

• 2 of 4 pups at P0 show clots in the heart; in neonates, spontaneous death is associated with major thrombosis in the heart

abnormal atrial thrombosis ( J:115658 )

• 6 of 16 adults show massive thrombosis in the atria and/or ventricles that is often associated with leukocyte infiltration

abnormal placental thrombosis ( J:115658 )

• severe thrombosis in the placenta of pregnant females, irrespective of the embryo genotype

growth/size/body

enlarged spleen ( J:115658 )

cardiovascular system

venoocclusion ( J:115658 )

• 3 of 14 adults show vessel occlusion in the lungs

• some show ocular vein occlusion

• 50% of sexually active males show occlusion of the dorsal penile vein

portal hypertension ( J:115658 )

• 12 of 15 adults show signs of portal hypertension, characterized by nodular regenerative hyperplasia, dilatation of the sinusoids and formation of shunt vessels

liver/biliary system

portal hypertension ( J:115658 )

• 12 of 15 adults show signs of portal hypertension, characterized by nodular regenerative hyperplasia, dilatation of the sinusoids and formation of shunt vessels

liver inflammation ( J:115658 )

• presence of neutrophil clusters in the sinusoids and of phagocytosing macrophages in the parenchyme, indicating in inflammatory response in the liver

abnormal liver morphology ( J:115658 )

• 2 of 4 one-day-old pups show infracted zones in the liver with coagulative necrosis, indicating impaired blood flow in the liver

hepatic necrosis ( J:115658 )

• coagulative necrosis in the liver

macrovesicular hepatic steatosis ( J:115658 )

• macrovesicular steatosis, the accumulation of fat in vesicles that displace the cytoplasm and distort the nucleus

abnormal liver regeneration ( J:115658 )

• liver shows nodular regenerative hyperplasia

immune system

enlarged spleen ( J:115658 )

liver inflammation ( J:115658 )

• presence of neutrophil clusters in the sinusoids and of phagocytosing macrophages in the parenchyme, indicating in inflammatory response in the liver

hematopoietic system

enlarged spleen ( J:115658 )

vision/eye

abnormal eye morphology ( J:115658 )

• 26% of males and 47% of females display severe degeneration of the eyes with blood accumulation in the front part of the eye

cornea perforation ( J:115658 )

• when eye degeneration is observed, occasional perforation of the cornea is seen

abnormal retina morphology ( J:115658 )

• when eye degeneration is observed, disruption of the retina is often seen

abnormal retina layer morphology ( J:115658 )

• in mutants with eye degeneration, the retinal layer is not seen

abnormal retina pigment epithelium morphology ( J:115658 )

• in mutants with eye degeneration, the pigment epithelium is not seen

abnormal sclera morphology ( J:115658 )

• in mutants with eye degeneration, the sclera is not seen

abnormal optic choroid morphology ( J:115658 )

• in mutants with eye degeneration, the choroid is not seen

reproductive system

abnormal penis morphology ( J:115658 )

♂ • severe thrombosis in the penile veins of sexually active males

priapism ( J:115658 )

♂ • 50% of all sexually active males develop irreversible priapism due to occlusion of the dorsal penile vein and impaired drainage and thrombosis of the corpora cavernosa

decreased litter size ( J:115658 )

• most likely due to placental thrombosis

renal/urinary system

abnormal penis morphology ( J:115658 )

♂ • severe thrombosis in the penile veins of sexually active males

pigmentation

abnormal retina pigment epithelium morphology ( J:115658 )

• in mutants with eye degeneration, the pigment epithelium is not seen

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
antithrombin III deficiency		DOID:3755	OMIM:613118	J:115658