Phenotypes associated with this allele

• Allele Symbol: Vwf^tm1Wgr
• Allele Name: targeted mutation 1, Denisa D Wagner
• Allele ID: MGI:2153009
• Summary: 8 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Vwf^tm1Wgr/Vwf^tm1Wgr	B6.129S2-Vwf^tm1Wgr	MGI:4834625
hm2	Vwf^tm1Wgr/Vwf^tm1Wgr	involves: 129S2/SvPas	MGI:4834657
hm3	Vwf^tm1Wgr/Vwf^tm1Wgr	involves: 129S2/SvPas * C57BL/6J	MGI:2653669
ht4	Vwf^tm1Wgr/Vwf^+	involves: 129S2/SvPas * C57BL/6J	MGI:3828999
cx5	Adamts13^tm1Dgi/Adamts13^tm1Dgi Vwf^tm1Wgr/Vwf^tm1Wgr	B6.129-Adamts13^tm1Dgi Vwf^tm1Wgr	MGI:4834630
cx6	Ldlr^tm1Her/Ldlr^tm1Her Vwf^tm1Wgr/Vwf^tm1Wgr	B6.129S-Vwf^tm1Wgr Ldlr^tm1Her	MGI:4834596
cx7	Fga^tm1Jld/Fga^tm1Jld Vwf^tm1Wgr/Vwf^tm1Wgr	involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6J	MGI:4834591
cx8	Adamts13^tm1Dgi/Adamts13^tm1Dgi Vwf^tm1Wgr/Vwf^tm1Wgr	involves: 129S2/SvPas * 129X1/SvJ * C57BL/6 * CASA/Rk	MGI:4834624

Genotype
MGI:4834625

hm1

• Allelic Composition: Vwf^tm1Wgr/Vwf^tm1Wgr
• Genetic Background: B6.129S2-Vwf^tm1Wgr

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

immune system

increased susceptibility to experimental autoimmune encephalomyelitis ( J:140334 )

• mice treated with MOG35-55, complete Freund's adjuvant (CFA), and pertussis toxin exhibit more severe clinical symptoms (lesions scores, demyelination, suppuration, mononuclear cellular infiltration, blood brain barrier permeability) in the brain and enhanced duration of the acute-early phase compared with similarly treated wild-type mice

• however, mice exhibit normal experimental autoimmune encephalomyelitis in the spinal cord and encephalitogenic T cell response

increased susceptibility to bacterial infection ( J:140334 )

• pertussis toxin-treated mice exhibit longer persistence of HA sensitization than similarly treated wild-type mice

• following treatment with complete Freund's adjuvant (CFA) and pertussis toxin, blood-brain barrier permeability is increased compared to in similarly treated wild-type mice

cardiovascular system

impaired blood-brain barrier function ( J:140334 )

• following treatment with MOG35-55, complete Freund's adjuvant (CFA), and pertussis toxin (PTX) or only CFA and PTX, blood-brain barrier permeability is increased compared to in similarly treated wild-type mice

homeostasis/metabolism

decreased susceptibility to induced thrombosis ( J:133469 )

• following FeCl3 injury, mice exhibit an increased time to clot formation and fail to completely occlude vessels unlike similarly treated wild-type mice

nervous system

impaired blood-brain barrier function ( J:140334 )

• following treatment with MOG35-55, complete Freund's adjuvant (CFA), and pertussis toxin (PTX) or only CFA and PTX, blood-brain barrier permeability is increased compared to in similarly treated wild-type mice

Genotype
MGI:4834657

hm2

• Allelic Composition: Vwf^tm1Wgr/Vwf^tm1Wgr
• Genetic Background: involves: 129S2/SvPas

homeostasis/metabolism

decreased myocardial infarct size ( J:148295 )

• following middle cerebral artery occlusion

decreased susceptibility to ischemic brain injury ( J:148295 )

• following middle cerebral artery occlusion, mice exhibit smaller infarct size and reduced neurological deficits compared with similarly treated wild-type mice

cardiovascular system

decreased myocardial infarct size ( J:148295 )

• following middle cerebral artery occlusion

nervous system

decreased susceptibility to ischemic brain injury ( J:148295 )

• following middle cerebral artery occlusion, mice exhibit smaller infarct size and reduced neurological deficits compared with similarly treated wild-type mice

Genotype
MGI:2653669

hm3

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

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

Genotype
MGI:3828999

ht4

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

homeostasis/metabolism

abnormal blood coagulation ( J:49083 )

• in heterozygotes, the activity level of coagulation FVIII was reduced to 57% of wild-type level

Genotype
MGI:4834630

cx5

• Allelic Composition: Adamts13^tm1Dgi/Adamts13^tm1Dgi; Vwf^tm1Wgr/Vwf^tm1Wgr
• Genetic Background: B6.129-Adamts13^tm1Dgi Vwf^tm1Wgr

hematopoietic system

hematopoietic system phenotype ( J:133469 )

N • mice exhibit the same LPS-induced thrombocytopenia as in Adamts13^tm1Dgi or Vwf^tm1Wgr homozygotes

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:133469 )

N • mice exhibit the same LPS-induced thrombocytopenia as in Adamts13^tm1Dgi or Vwf^tm1Wgr homozygotes

decreased susceptibility to induced thrombosis ( J:133469 )

• following FeCl3 injury, mice exhibit an increased time to clot formation and fail to completely occlude vessels unlike similarly treated wild-type mice

Genotype
MGI:4834596

cx6

• Allelic Composition: Ldlr^tm1Her/Ldlr^tm1Her; Vwf^tm1Wgr/Vwf^tm1Wgr
• Genetic Background: B6.129S-Vwf^tm1Wgr Ldlr^tm1Her

cardiovascular system

decreased susceptibility to atherosclerosis ( J:106677 )

• at 22 weeks, mice fed an atherogenic diet exhibit decreased atherosclerotic lesions size with fewer macrophages and reduced calcification compared with similarly treated Ldlr^tm1Her homozygotes

• lesions in mice fed an atherogenic diet are uniformly distributed unlike in similarly treated Ldlr^tm1Her homozygotes that exhibit formation hot spots

• however, mice exhibit normal atherosclerotic lesions at 37 weeks

immune system

impaired leukocyte tethering or rolling ( J:106677 )

• however, rolling on an atherogenic diet is normal

• leukocyte rolling on a chow diet is decreased compared to in wild-type mice

cellular

impaired leukocyte tethering or rolling ( J:106677 )

• leukocyte rolling on a chow diet is decreased compared to in wild-type mice

• however, rolling on an atherogenic diet is normal

hematopoietic system

impaired leukocyte tethering or rolling ( J:106677 )

• leukocyte rolling on a chow diet is decreased compared to in wild-type mice

• however, rolling on an atherogenic diet is normal

Genotype
MGI:4834591

cx7

• Allelic Composition: Fga^tm1Jld/Fga^tm1Jld; Vwf^tm1Wgr/Vwf^tm1Wgr
• Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6J

mortality/aging

postnatal lethality, incomplete penetrance ( J:63750 )

• 23% of mice die before weaning

homeostasis/metabolism

abnormal blood coagulation ( J:63750 )

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

• thrombi that form in FeCl3-treated mice fail to resist sheer stress and eventually break off unlike in similarly treated wild-type mice

• FeCl3-induced thrombi are more fragile than in similarly treated wild-type mice or Fga^tm1Jld homozygotes

• FeCl3-treated mice exhibit shorter occlusion times compared with similarly treated Vwf^tm1Wgr homozygotes

Genotype
MGI:4834624

cx8

• Allelic Composition: Adamts13^tm1Dgi/Adamts13^tm1Dgi; Vwf^tm1Wgr/Vwf^tm1Wgr
• Genetic Background: involves: 129S2/SvPas * 129X1/SvJ * C57BL/6 * CASA/Rk

mortality/aging

decreased susceptibility to xenobiotic induced morbidity/mortality ( J:133469 )

• in shigatoxin (Stx)-treated mice

homeostasis/metabolism

decreased susceptibility to xenobiotic induced morbidity/mortality ( J:133469 )

• in shigatoxin (Stx)-treated mice

decreased physiological sensitivity to xenobiotic ( J:133469 )

• shigatoxin (Stx)-treated mice exhibit less severe thrombocytopenia and reduced mortality compared with similarly treated Adamts13^tm1Dgi homozygotes

hematopoietic system

abnormal platelet morphology ( J:133469 )

• shigatoxin (Stx)-treated mice exhibit less severe thrombocytopenia and reduced mortality compared with similarly treated Adamts13^tm1Dgi homozygotes