All Phenotypes Thbd<tm2Rdr> MGI Mouse

Phenotypes associated with this allele

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Thbd^tm2Rdr/Thbd^tm2Rdr	involves: 129S2/SvPas * C57BL/6	MGI:2653098
ht2	Thbd^tm1Wlr/Thbd^tm2Rdr	involves: 129S2/SvPas * C57BL/6	MGI:3844986
cn3	Tg(Tek-cre)1Ywa/0 Thbd^tm2Rdr/Thbd^tm2Wlr	involves: 129S2/SvPas * C57BL/6 * SJL	MGI:3844980
cx4	Fga^tm1Jld/Fga^tm1Jld Thbd^tm2Rdr/Thbd^tm2Rdr	involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6	MGI:2653115
cx5	Plau^tm1Mlg/Plau^tm1Mlg Thbd^tm2Rdr/Thbd^tm2Rdr	involves: 129S2/SvPas	MGI:3844987
cx6	Plat^tm1Mlg/Plat^tm1Mlg Thbd^tm2Rdr/Thbd^tm2Rdr	involves: 129S2/SvPas	MGI:3844988
cx7	F3^tm1Dco/F3^tm1Dco Thbd^tm2Rdr/Thbd^tm2Rdr	involves: 129S2/SvPas * C57BL/6	MGI:2653104
cx8	F3^tm1Dco/F3^tm1Dco Thbd^tm2Rdr/Thbd^tm2Rdr Tg(F3)1Nmk/0	involves: 129/Sv * 129S2/SvPas * BALB/c * C57BL/6	MGI:3687574

Allelic Composition	Thbd^tm2Rdr/Thbd^tm2Rdr
Genetic Background	involves: 129S2/SvPas * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Thbd^tm2Rdr mutation (0 available); any Thbd mutation (25 available)

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

mortality/aging

embryonic lethality, complete penetrance ( J:74855 )

• homozygotes are completely resorbed by E9.5

embryo

embryonic growth arrest ( J:74855 , J:82224 )

• homozygotes exhibit an overall growth retardation at E8.5, followed by rapid resorption within the next 10-12 hrs (J:74855)

• anti-coagulation treatment of pregnant mothers with heparin or warfarin does not overcome the growth defect, with E9.5 homozygotes resembling E8.5 wild-type mice (J:82224)

small ectoplacental cone ( J:82224 )

• at E8.5, homozygotes contain a reduced number of diploid ectoplacental trophoblast cells (63.5% of wild-type), as a result of reduced cell proliferation

• anti-coagulation therapy with heparin or warfarin does not overcome the growth defect in the ectoplacental cone

• growth arrest of trophoblast cells is not mediated by fibrin, but is a likely result of engagement of protease-activated receptors by coagulation factors

abnormal trophoblast layer morphology ( J:82224 )

• at E8.5, BrdU incorporation is marginally lower in mutant polyploid giant trophoblast cells, but is significantly reduced in diploid trophoblast cells of the ectoplacental cone

decreased trophoblast giant cell number ( J:82224 )

• at E8.5, all homozygotes exhibit a significant increase in TUNEL+ giant trophoblast cells but only rarely in ectoplacental cone cells, indicating selective cell death of giant trophoblast cells

• at E8.5, BrdU incorporation is only marginally reduced in mutant polyploid giant trophoblast cells

• anti-coagulation treatment of pregnant mothers with heparin or warfarin inhibits cell death of giant trophoblast cells

• death of giant trophoblast cells is caused by conversion of the thrombin substrate fibrinogen to fibrin and subsequent formation of fibrin degradation products

abnormal placenta development ( J:82224 )

Allelic Composition	Thbd^tm1Wlr/Thbd^tm2Rdr
Genetic Background	involves: 129S2/SvPas * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Thbd^tm1Wlr mutation (0 available); any Thbd mutation (25 available)
Thbd^tm2Rdr mutation (0 available); any Thbd mutation (25 available)

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

cardiovascular system

abnormal heart morphology ( J:47676 , J:111502 )

• fibrin deposition is increased 10- to 20-fold compared to in wild-type mice (J:47676)

• fibrin deposition is increased compared to in wild-type mice (J:111502)

immune system

abnormal spleen morphology ( J:47676 , J:111502 )

• fibrin deposition is increased 10- to 20-fold compared to in wild-type mice (J:47676)

• fibrin deposition is increased compared to in wild-type mice (J:111502)

respiratory system

abnormal lung morphology ( J:47676 , J:111502 )

• fibrin deposition is increased 10- to 20-fold compared to in wild-type mice (J:47676)

• fibrin deposition is increased compared to in wild-type mice (J:111502)

homeostasis/metabolism

increased circulating D-dimer level ( J:111502 )

• plasma D-dimer levels are increased compared to in wild-type mice

abnormal blood coagulation ( J:111502 )

• plasma thrombin-antithrombin (TAT) and D-dimer are increased compared to in wild-type mice

abnormal lung thrombosis ( J:47676 )

• under hypoxic conditions, mice exhibit a 10-fold increase in fibrin depositions in the lung compared with a 4- to 5-fold increase in similarly treated wild-type mice

increased susceptibility to induced thrombosis ( J:111502 )

• after FeCl3-induced injury mice exhibit accelerated arterial thrombus growth compared with wild-type mice

hematopoietic system

abnormal spleen morphology ( J:47676 , J:111502 )

• fibrin deposition is increased 10- to 20-fold compared to in wild-type mice (J:47676)

• fibrin deposition is increased compared to in wild-type mice (J:111502)

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

Venous and arterial thrombi and extravascular fibrinogen deposition in the lungs of Thbd^tm2Rdr/Thbd^tm2Wlr Tg(Tek-cre)1Ywa/0 mice

mortality/aging

premature death ( J:71269 )

• 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

lethality throughout fetal growth and development, incomplete penetrance ( J:71269 )

• although present in Mendelian ratios at E9.5 and E10.5, fewer than expected mice are present at E14.5 and E16.5

embryonic lethality during organogenesis, incomplete penetrance ( J:71269 )

• 40% of mice die around E10.5

reproductive system

priapism ( J:71269 )

• in 8% of male mice and occasionally associated with necrosis of testis

cardiovascular system

enlarged heart ( J:71269 )

• at 5 to 8 weeks

increased heart weight ( J:71269 )

• beginning at 3 weeks of age

increased heart right ventricle weight ( J:71269 )

cardiac fibrosis ( J:71269 )

• at 8 weeks, mice develop multifoci myocardial fibrosis unlike wild-type mice

hemothorax ( J:71269 )

• some mice exhibit lethal intrathoracic hemorrhaging unlike wild-type mice

• warfarin treatment fails to improve overall survival in these mice

lung hemorrhage ( J:71269 )

• in 10% of mice

gastrointestinal hemorrhage ( J:71269 )

• in 8% of mice

intracerebral hemorrhage ( J:71269 )

• some mice exhibit lethal cerebral hemorrhaging unlike wild-type mice

• warfarin treatment fail to improve overall survival in these mice

liver hemorrhage ( J:71269 )

skin hemorrhage ( J:71269 )

• 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

pulmonary hypertension ( J:71269 )

• due to increased resistance in the pulmonary vascular bed as a consequence of recurrent embolic and/or vascular lung injury

homeostasis/metabolism

increased circulating D-dimer level ( J:71269 )

• plasma D-Dimer levels are increased at 3, 5, and 8 weeks compared to in wild-type mice

increased circulating interleukin-6 level ( J:71269 )

• in older mice due to widespread organ damage

abnormal blood coagulation ( J:71269 )

• 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

abnormal thrombosis ( J:71269 )

• 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

abnormal placental thrombosis ( J:71269 )

• at E10.5, 36% of mice exhibit pallor or placenta thrombosis unlike wild-type mice

abnormal acute phase protein level ( J:71269 )

• 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

hematuria ( J:71269 )

• in 1% of mice

respiratory system

hemothorax ( J:71269 )

• some mice exhibit lethal intrathoracic hemorrhaging unlike wild-type mice

• warfarin treatment fails to improve overall survival in these mice

lung hemorrhage ( J:71269 )

• in 10% of mice

abnormal lung morphology ( J:71269 )

• 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

hematopoietic system

increased spleen weight ( J:71269 )

• 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

increased megakaryocyte cell number ( J:71269 )

• at 8 weeks, the number of megakaryocytes per splenocytes is increased compared to in wild-type mice

thrombocytopenia ( J:71269 )

• at 3 weeks, mice exhibit lower than normal platelet counts

• however, platelet counts are normalized in older mice due to compensation

immune system

increased spleen weight ( J:71269 )

• 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

increased circulating interleukin-6 level ( J:71269 )

• in older mice due to widespread organ damage

abnormal acute phase protein level ( J:71269 )

• 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

growth/size/body

enlarged heart ( J:71269 )

• at 5 to 8 weeks

increased heart weight ( J:71269 )

• beginning at 3 weeks of age

decreased body size ( J:71269 )

• after weaning, 14% of mice are runted

decreased body weight ( J:71269 )

• 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

slow postnatal weight gain ( J:71269 )

• over the 8 weeks following weaning

increased spleen weight ( J:71269 )

• 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

liver/biliary system

liver hemorrhage ( J:71269 )

abnormal liver morphology ( J:71269 )

• 36% of mice exhibit liver lesions consisting of liver infarcts or hemorrhagic liver swellings unlike wild-type mice

renal/urinary system

hematuria ( J:71269 )

• in 1% of mice

digestive/alimentary system

gastrointestinal hemorrhage ( J:71269 )

• in 8% of mice

integument

skin hemorrhage ( J:71269 )

• 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

pallor ( J:71269 )

• at E10.5, 36% of mice exhibit pallor or placenta thrombosis unlike wild-type mice

nervous system

intracerebral hemorrhage ( J:71269 )

• some mice exhibit lethal cerebral hemorrhaging unlike wild-type mice

• warfarin treatment fail to improve overall survival in these mice

Allelic Composition	Fga^tm1Jld/Fga^tm1Jld Thbd^tm2Rdr/Thbd^tm2Rdr
Genetic Background	involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Fga^tm1Jld mutation (0 available); any Fga mutation (44 available)
Thbd^tm2Rdr mutation (0 available); any Thbd mutation (25 available)

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:82224 )

• unlike Thbd^tm2Rdr homozygotes which are completely resorbed by E9.5, double homozygotes are recovered as late as E10.5

embryo

embryonic growth arrest ( J:82224 )

• double homozygotes exhibit embryonic growth arrest at E8.5

• inhibition of fibrinolysis with tranexamic acid has the same effect as complete elimination of fibrinogen and results in recovery of growth-arrested embryos at E9.5

small ectoplacental cone ( J:82224 )

• double homozygotes display a proliferation defect in trophoblast cells of the ectoplacental cone

• similarly, inhibition of fibrinolysis with tranexamic acid fails to augment proliferation of ectoplacental trophoblast cells

• in contrast, both the absence of fibrinogen and inhibition of fibrinolysis prevents DNA fragmentation in trophoblast giant cells, as detected by TUNEL assay

Allelic Composition	Plau^tm1Mlg/Plau^tm1Mlg Thbd^tm2Rdr/Thbd^tm2Rdr
Genetic Background	involves: 129S2/SvPas

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Plau^tm1Mlg mutation (3 available); any Plau mutation (29 available)
Thbd^tm2Rdr mutation (0 available); any Thbd mutation (25 available)

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

mortality/aging

embryonic lethality ( J:47676 )

Allelic Composition	Plat^tm1Mlg/Plat^tm1Mlg Thbd^tm2Rdr/Thbd^tm2Rdr
Genetic Background	involves: 129S2/SvPas

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Plat^tm1Mlg mutation (5 available); any Plat mutation (60 available)
Thbd^tm2Rdr mutation (0 available); any Thbd mutation (25 available)

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

mortality/aging

embryonic lethality ( J:47676 )

Allelic Composition	F3^tm1Dco/F3^tm1Dco Thbd^tm2Rdr/Thbd^tm2Rdr
Genetic Background	involves: 129S2/SvPas * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
F3^tm1Dco mutation (0 available); any F3 mutation (24 available)
Thbd^tm2Rdr mutation (0 available); any Thbd mutation (25 available)

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:82224 )

• unlike Thbd^tm2Rdr homozygotes which are completely resorbed by E9.5, double homozygotes develop normally until E9.5 but become necrotic by E10.5 due to defective yolk sac vasculature

embryo

abnormal vitelline vasculature morphology ( J:82224 )

• by E10.5, double homozygotes display defective vitelline vasculature with free blood pools in the yolk sac cavity

absent vitelline blood vessels ( J:82224 )

• by E10.5, double mutant yolk sacs lack blood-filled larger vitelline vessels

cardiovascular system

abnormal vitelline vasculature morphology ( J:82224 )

• by E10.5, double homozygotes display defective vitelline vasculature with free blood pools in the yolk sac cavity

absent vitelline blood vessels ( J:82224 )

• by E10.5, double mutant yolk sacs lack blood-filled larger vitelline vessels

abnormal pericardial cavity morphology ( J:82224 )

• by E10.5, double homozygotes exhibit an enlarged pericardial cavity, similar to F3^tm1Dco homozygotes

Allelic Composition	F3^tm1Dco/F3^tm1Dco Thbd^tm2Rdr/Thbd^tm2Rdr Tg(F3)1Nmk/0
Genetic Background	involves: 129/Sv * 129S2/SvPas * BALB/c * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
F3^tm1Dco mutation (0 available); any F3 mutation (24 available)
Tg(F3)1Nmk mutation (0 available)
Thbd^tm2Rdr mutation (0 available); any Thbd mutation (25 available)

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

mortality/aging

mortality/aging ( J:82224 )

N	• mutant embryos develop normally beyond E10.5 and are viable to birth

embryo

placenta hemorrhage ( J:82224 )

• at E10.5, mutant embryos exhibit bleeding in the placental labyrinth, not caused by thrombomodulin deficiency but characteristic of embryos with low F3 activity

cardiovascular system

placenta hemorrhage ( J:82224 )

• at E10.5, mutant embryos exhibit bleeding in the placental labyrinth, not caused by thrombomodulin deficiency but characteristic of embryos with low F3 activity

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