mortality/aging
|
• frequently die within 24 hours after birth
|
|
• only 60% reach weaning age
|
|
• beyond weaning, survival remains compromised with death at various ages and only about 30% survival beyond 6 months
|
homeostasis/metabolism
|
• plasma displays low heparin cofactor activity
• 2 of 4 pups at P0 show clots in the heart
|
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
• in neonates, spontaneous death is associated with major thrombosis in the heart
• 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
|
|
• 6 of 16 adults show massive thrombosis in the atria and/or ventricles that is often associated with leukocyte infiltration
|
cardiovascular system
|
• 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
|
|
• all show massive thrombosis in the heart
• 2 of 4 pups at P0 show clots in the heart
|
|
• 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
|
• 12 of 15 adults show signs of portal hypertension, characterized by nodular regenerative hyperplasia, dilatation of the sinusoids and formation of shunt vessels
|
|
• presence of neutrophil clusters in the sinusoids and of phagocytosing macrophages in the parenchyme, indicating in inflammatory response in the liver
|
|
• 2 of 4 one-day-old pups show infracted zones in the liver with coagulative necrosis, indicating impaired blood flow in the liver
|
|
• coagulative necrosis in the liver
|
|
• macrovesicular steatosis, the accumulation of fat in vesicles that displace the cytoplasm and distort the nucleus
|
|
• liver shows nodular regenerative hyperplasia
|
immune system
|
• presence of neutrophil clusters in the sinusoids and of phagocytosing macrophages in the parenchyme, indicating in inflammatory response in the liver
|
hematopoietic system
vision/eye
|
• 26% of males and 47% of females display severe degeneration of the eyes with blood accumulation in the front part of the eye
|
|
• in mutants with eye degeneration, the pigment epithelium is not seen
|
|
• when eye degeneration is observed, occasional perforation of the cornea is seen
|
|
• in mutants with eye degeneration, the choroid is not seen
|
|
• when eye degeneration is observed, disruption of the retina is often seen
|
|
• in mutants with eye degeneration, the retinal layer is not seen
|
|
• in mutants with eye degeneration, the sclera is not seen
|
embryogenesis
|
• severe thrombosis in the placenta of pregnant females, irrespective of the embryo genotype
|
reproductive system
 |
• severe thrombosis in the penile veins of sexually active males
(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
(J:115658)
|
|
• most likely due to placental thrombosis
|
renal/urinary system
|
|
• severe thrombosis in the penile veins of sexually active males
(J:115658)
|
pigmentation
|
• in mutants with eye degeneration, the pigment epithelium is not seen
|
Mouse Models of Human Disease |
OMIM ID | Ref(s) | |
| Antithrombin III Deficiency; AT3D | 613118 | J:115658 | |