Phenotypes Associated with This Genotype

Genotype
MGI:2653669

• Allelic Composition: Vwf^tm1Wgr/Vwf^tm1Wgr
• Genetic Background: involves: 129S2/SvPas * C57BL/6J

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

Spontaneous bleeding events in Vwf^tm1Wgr/Vwf^tm1Wgr mice

cardiovascular system

internal hemorrhage ( J:49083 )

• ~10% of newborn homozygotes displayed spontaneous intra-abdominal bleeding

• in some cases, bleeding was massive and proved fatal

• after the neonatal period, no obvious spontaneous bleeding was observed, and females survived pregnancy and delivery of normal size litters

homeostasis/metabolism

abnormal blood coagulation ( J:49083 )

• the activity level of coagulation FVIII was reduced to 20% of wild-type level

• however, platelet, red cell and white cell counts, hematocrit, and hemoglobin were all within normal range

abnormal platelet physiology ( J:49083 )

• at 10 min after ferric chloride-induced injury, most mutant arterioles (66.6%) showed very few, if any, platelet interactions with the vessel wall, whereas all of wild-type arterioles exhibited either complete occlusion (25%) or numerous platelet interactions with the vessel wall, including formation of thrombi

decreased susceptibility to induced thrombosis ( J:63750 )

• after FeCl3 treatment, platelet interaction with the vessel wall is delayed and platelet deposition is 5-fold less than in similarly treated wild-type mice

• after FeCl3 treatment, thrombi fail to occlude blood vessels unlike in similarly treated wild-type mice

increased bleeding time ( J:49083 )

• following amputation of a tail segment, homozygotes exhibited a significantly prolonged bleeding time relative to wild-type mice (499 33.4 sec versus 69.7 5.2 sec, respectively)

• only 5 of 21 homozygotes managed to control their blood loss without cauterization

• in addition, 2 anesthetized animals that were not cauterized were never able to control their bleeding

increased partial thromboplastin time ( J:49083 )

• consistent with a reduction in FVIII, the activated partial thromboplastin time (aPTT) was prolonged

• however, prothrombin time was normal

digestive/alimentary system

melena ( J:49083 )

• 7.2% of adult homozygotes displayed the presence of fecal occult blood

hematopoietic system

abnormal platelet physiology ( J:49083 )

• at 10 min after ferric chloride-induced injury, most mutant arterioles (66.6%) showed very few, if any, platelet interactions with the vessel wall, whereas all of wild-type arterioles exhibited either complete occlusion (25%) or numerous platelet interactions with the vessel wall, including formation of thrombi