Phenotypes associated with this allele

• Allele Symbol: F7^tm1Pec
• Allele Name: targeted mutation 1, Peter Carmeliet
• Allele ID: MGI:2182766
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	F7^tm1Pec/F7^tm1Pec	involves: 129X1/SvJ * C57BL/6J	MGI:3039943
ht2	F7^tm1Pec/F7^+	involves: 129X1/SvJ * C57BL/6J	MGI:3039944
ht3	F7^tm1(tTA,tetO-F7)Edr/F7^tm1Pec	involves: 129X1/SvJ * C57BL/6	MGI:3831196
cx4	F7^tm1Pec/F7^tm1Pec Proc^tm1Fjc/Proc^tm1Fjc	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:4839937
cx5	F7^tm1Pec/F7^+ Proc^tm1Fjc/Proc^tm1Fjc	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:4839992
cx6	F7^tm1Pec/F7^+ Tfpi^tm1Gjb/Tfpi^tm1Gjb	involves: 129X1/SvJ * C57BL/6	MGI:3040067
cx7	F7^tm1Pec/F7^tm1Pec Tfpi^tm1Gjb/Tfpi^tm1Gjb	involves: 129X1/SvJ * C57BL/6	MGI:3040068

Genotype
MGI:3039943

hm1

• Allelic Composition: F7^tm1Pec/F7^tm1Pec
• Genetic Background: involves: 129X1/SvJ * C57BL/6J

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

mortality/aging

neonatal lethality, incomplete penetrance ( J:44294 )

• homozygous mutant mice developed normally through embryogenesis; however, 70% of homozygous neonates died from fatal intra-abdominal bleeding within 24 hours after birth

• most of the remaining neonates died from intracranial hemorrhage before the age of 24 days

cardiovascular system

cardiovascular system phenotype ( J:44294 )

N • all homozygous mutant embryos displayed normal vascular development at all embryonic stages examined: no vascular fragility was observed in the yolk sac or in the embryo itself

N • homozygous mutant mice displayed normal blood vessel formation, as shown by intact von Willebrand Factor immunoreactive endothelium and numerous alpha-actin-positive smooth muscle cells

N • other components of the intrinsic or extrinsic coagulation cascade appeared normal

N • maternal-fetal transfer could only be detected after E9.5 and at supraphysiological maternal plasma levels

internal hemorrhage ( J:44294 )

• hematoxylin/eosin staining of abdominal sections revealed extensive extravasation of red blood cells into the peritoneal cavity, with concomitant anemia in the surrounding organs

Genotype
MGI:3039944

ht2

• Allelic Composition: F7^tm1Pec/F7⁺
• Genetic Background: involves: 129X1/SvJ * C57BL/6J

normal phenotype

no abnormal phenotype detected ( J:44294 )

• heterozygous mutant neonates displayed approximately 10% of adult plasma activity levels, and were protected against bleeding and perinatal lethality

Genotype
MGI:3831196

ht3

• Allelic Composition: F7^{tm1(tTA,tetO-F7)Edr}/F7^tm1Pec
• Genetic Background: involves: 129X1/SvJ * C57BL/6

mortality/aging

premature death ( J:144540 )

• about 50% of mice die between 3 and 10 weeks of age

Genotype
MGI:4839937

cx4

• Allelic Composition: F7^tm1Pec/F7^tm1Pec; Proc^tm1Fjc/Proc^tm1Fjc
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Hemorrhage and edema in F7^tm1Pec/F7^tm1Pec Proc^tm1Fjc/Proc^tm1Fjc mice

mortality/aging

neonatal lethality, complete penetrance ( J:61481 )

• genotyping analysis indicated that, at E17.5 dpc, double homozygous mutant embryos were present at the expected Mendelian frequency; however, double homozygous mutant neonates died immediately after birth

cardiovascular system

abnormal dorsal aorta morphology ( J:61481 )

• fibrin deposition is observed at E12.5

hemorrhage ( J:61481 )

• all E14.5 dpc double mutant embryos displayed extensive peripheral and internal bleeding and fibrin deposition, with concomitant anemia

• at E14.5 and E17.5, yolk sac development and blood flow generally appeared normal; however, one out of five embryos studied showed blood pools within the amniotic sac

• at E14.5, fibrin deposition, hemorrhage, and tissue degradation was observed in the brain, along the spine, and in the liver; blood could not be collected by intracardiac puncture due to massive hemorrhaging

• at E17.5 dpc, four of five embryos were alive, but displayed severe edema, anemia, subcutaneous bleeding at the joints, and peripheral bleeding, as well as necrosis around the nasal area; no hemorrhage was observed in the mutant placenta

• at E17.5, fibrotic patches were observed in the liver, and variable bleeding and necrosis was found in the brain; in one case, bleeding was also evident in the stomach and intestinal tract

• at E17.5, the ventricles were anemic, and the atria were clotted displaying abnormal collagen invasion in the internal atrial tissue

• at E17.5, interstitial fibrin deposition was also seen in areas surrounding fibrotic lesions

• In contrast to the E14.5 dpc and E17.5 dpc time points, E12.5 dpc double homozygous mutant embryos appeared developmentally normal, with no obvious external bleeding anomalies; however, fibrin deposition, in the absence of hemorrhage, was noted in the liver interstitia and in vessels in the brain, neural canal, caudal artery, pulmonary cavity, dorsal aorta, and left hind-limb bud

• areas of intra- and extravascular fibrin deposition did not stain positively for P-selectin-positive activated platelets

homeostasis/metabolism

abnormal blood coagulation ( J:61481 )

• double homozygous mutant embryos exhibited an intra- and extravascular progressive coagulopathy as early as E14.5 dpc

hydrops fetalis ( J:61481 )

• peripheral edema by E17.5

Genotype
MGI:4839992

cx5

• Allelic Composition: F7^tm1Pec/F7⁺; Proc^tm1Fjc/Proc^tm1Fjc
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

mortality/aging

neonatal lethality, complete penetrance ( J:61481 )

• compound mutant embryos were present at their expected Mendelian frequency

• compound mutant mice were born but succumbed to consumptive coagulopathy

• postnatal underrepresentation was due to the inability to identify these neonates before their death and consumption by their parents

cardiovascular system

internal hemorrhage ( J:61481 )

• the liver, brain, and atria of these compound mutant mice showed a similar hemorrhage, fibrin deposition, and inflammatory cell infiltration as double homozygous mutant embryos; however no severe edema or peripheral bleeding were observed

• at E14.5 dpc, 2 out of 7 compound mutant mice displayed variable bleeding spots on the skin and blood pools within the amniotic sac; interstitial fibrin deposition was detected in the liver, and to a lesser extent in the brain, in the absence of peripheral hemorrhage

homeostasis/metabolism

abnormal blood coagulation ( J:61481 )

• compound mutant embryos displayed an organ coagulopathy similar to that observed in double homozygous mutant embryos

Genotype
MGI:3040067

cx6

• Allelic Composition: F7^tm1Pec/F7⁺; Tfpi^tm1Gjb/Tfpi^tm1Gjb
• Genetic Background: involves: 129X1/SvJ * C57BL/6

mortality/aging

neonatal lethality, complete penetrance ( J:89395 )

• these compound mutant mice were also rescued from intrauterine lethality, and were fully represented at E17.5

• however, despite normal organ develeopment, compound neonates were either found dead or died immediately after birth

cardiovascular system

internal hemorrhage ( J:89395 )

• as early as E9.5, compound mutant mice exhibited thrombosis and hemorrhage from occluded vessels in the brain with subsequent necrosis of surrounding tissue

• at this stage, compound mutant mice also displayed diffuse fibrin deposition in the interstitia of the liver

homeostasis/metabolism

abnormal blood coagulation ( J:89395 )

• compound mutant mice succumbed to perinatal consumptive coagulopathy

• compound mutant mice showed signs of disseminated intravascular coagulation in the kidneys after birth

Genotype
MGI:3040068

cx7

• Allelic Composition: F7^tm1Pec/F7^tm1Pec; Tfpi^tm1Gjb/Tfpi^tm1Gjb
• Genetic Background: involves: 129X1/SvJ * C57BL/6

mortality/aging

neonatal lethality, complete penetrance ( J:89395 )

• double homozygous mutant mice were rescued from intrauterine death

• double homozygous mutant mice developed normally in utero and survived to birth but suffered from fatal postnatal bleeding events