Analysis Tools
mortality/aging
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• by 25 weeks of age, most mice die secondary to consumptive coagulopathy or progressive thrombosis, hemorrhage/necrosis of individual digits, extremities, skin, ears, tongue, or priapism
• male mice exhibit shorter life spans compared with female mice (100% at 20 and 30 weeks, respectively)
• unlike wild-type mice, some mice develop lethal cerebral or intrathoracic hemorrhaging that cannot be prevented by warfarin treatment
• however, gonadectomized mice do not display any gender-specific difference in life span
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• although present in Mendelian ratios at E9.5 and E10.5, fewer than expected mice are present at E14.5 and E16.5
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• 40% of mice die around E10.5
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reproductive system
cardiovascular system
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• at 5 to 8 weeks
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• beginning at 3 weeks of age
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• at 8 weeks, mice develop multifoci myocardial fibrosis unlike wild-type mice
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hemothorax
(
J:71269
)
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• some mice exhibit lethal intrathoracic hemorrhaging unlike wild-type mice
• warfarin treatment fails to improve overall survival in these mice
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• in 10% of mice
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• in 8% of mice
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• some mice exhibit lethal cerebral hemorrhaging unlike wild-type mice
• warfarin treatment fail to improve overall survival in these mice
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• early skin lesions on extremities, hindlimbs, the perianal region, abdominal skin, and ears consist of small hemorrhagic lesions that increase in size and become necrotic
• 67% of mice exhibit subcutaneous hemorrhage unlike wild-type mice
• however, treatment with warfarin between 3 and 11 weeks prevents development of hemorrhagic or necrotic skin lesions
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• due to increased resistance in the pulmonary vascular bed as a consequence of recurrent embolic and/or vascular lung injury
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homeostasis/metabolism
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• plasma D-Dimer levels are increased at 3, 5, and 8 weeks compared to in wild-type mice
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• in older mice due to widespread organ damage
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• in terminal mice, whole-blood clotting time is prolonged compared to in wild-type mice and 6 mice fail to form clots within 60 minutes
• plasma levels of thrombin-antithrombin (TAT) complexes and D-Dimer are increased at 3, 5, and 8 weeks compared to in wild-type mice
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• mice develop age- and gender-dependent progression of thrombosis that leads to lethal consumptive coagulopathy
• mice exhibit multiple venous and arterial thrombi that are fibrin-rich with few cellular components
• however, no thrombi occur in the cardiac atria and treatment with warfarin between 3 and 11 weeks prevents thrombosis
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• at E10.5, 36% of mice exhibit pallor or placenta thrombosis unlike wild-type mice
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• fibrinogen deposits in the lungs are increased compared to in wild-type mice
• at 3 weeks, mice exhibit increased consumption of fibrinogen compared to wild-type mice
• however, fibrinogen levels increased in older mice due to compensation
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respiratory system
hemothorax
(
J:71269
)
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• some mice exhibit lethal intrathoracic hemorrhaging unlike wild-type mice
• warfarin treatment fails to improve overall survival in these mice
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• in 10% of mice
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• at 3 weeks, lungs have increased extravascular fibrinogen depositions compared to in wild-type mice associated with increased extracellular matrix and a disruption of the tissue architecture resulting in distention of terminal airways and alveoli, destruction of the alveolar septa, and, in severe cases, formation of bullae
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hematopoietic system
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• at 8 weeks, mice exhibit increased spleen weight compared to in wild-type mice
• however, treatment with warfarin between 3 and 11 weeks prevents increased spleen weight
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• at 8 weeks, the number of megakaryocytes per splenocytes is increased compared to in wild-type mice
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• at 3 weeks, mice exhibit lower than normal platelet counts
• however, platelet counts are normalized in older mice due to compensation
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immune system
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• at 8 weeks, mice exhibit increased spleen weight compared to in wild-type mice
• however, treatment with warfarin between 3 and 11 weeks prevents increased spleen weight
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• in older mice due to widespread organ damage
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• fibrinogen deposits in the lungs are increased compared to in wild-type mice
• at 3 weeks, mice exhibit increased consumption of fibrinogen compared to wild-type mice
• however, fibrinogen levels increased in older mice due to compensation
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growth/size/body
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• at 5 to 8 weeks
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• beginning at 3 weeks of age
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• after weaning, 14% of mice are runted
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• from the first week after birth through 8 weeks post-weaning, mice exhibit decreased body weight
• however, treatment with warfarin between 3 and 11 weeks prevents reduced body weight
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• over the 8 weeks following weaning
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• at 8 weeks, mice exhibit increased spleen weight compared to in wild-type mice
• however, treatment with warfarin between 3 and 11 weeks prevents increased spleen weight
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liver/biliary system
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• 36% of mice exhibit liver lesions consisting of liver infarcts or hemorrhagic liver swellings unlike wild-type mice
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renal/urinary system
digestive/alimentary system
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• in 8% of mice
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integument
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• early skin lesions on extremities, hindlimbs, the perianal region, abdominal skin, and ears consist of small hemorrhagic lesions that increase in size and become necrotic
• 67% of mice exhibit subcutaneous hemorrhage unlike wild-type mice
• however, treatment with warfarin between 3 and 11 weeks prevents development of hemorrhagic or necrotic skin lesions
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• at E10.5, 36% of mice exhibit pallor or placenta thrombosis unlike wild-type mice
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nervous system
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• some mice exhibit lethal cerebral hemorrhaging unlike wild-type mice
• warfarin treatment fail to improve overall survival in these mice
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