Table 3.

Results of coagulation factor gene disruption in mice

Deficiency	Knockout mouse model	Reference
Fibrinogen	Fga: Mice homozygous for disruptions of this gene have blood that is unable to clot. On some genetic backgrounds, this can lead to fatal bleeding.
	Fgg: Pregnant homozygous null mice exhibit retarded embryoplacental development, spontaneous abortion, and maternal death through excessive uterine bleeding. Mutants expressing a truncated polypeptide show reduced platelet aggregation, increased bleeding time, and occasional fatal neonatal bleeding.	39,40
Prothrombin	Partial embryonic lethality (E9.5-E11.5).	41,42
	Not compatible with survival to adulthood.
	Neonatal hemorrhage, no survival beyond several days, loss of vascular integrity.
Factor V	Half of mice homozygous for a null allele die at E9 to E10 with defects in yolk-sac vasculature and somite formation; the remaining half develop to term but die of massive hemorrhage within hours of birth.	43
Factor V and Factor VIII	Levels of plasma FV and FVIII are all reduced to 50% of wild-type in Lman1 KO mice, compared with the 5% to 30% levels typically observed in human F5F8D patients. Lack of a significant bleeding phenotype.
	Partial lethal phenotype was observed in Lman1 KO mice only on certain genetic backgrounds.	44
Factor VII	No embryonic lethality.
	Not compatible with survival to adulthood.	45-47
	Normal embryonic development, death caused by hemorrhage in neonates, no survival beyond 24 d, no vascular defects.
Factor X	Partial embryonic lethality (E11.5-E12.5).
	Complete absence of FX is incompatible with murine survival to adulthood but minimal FX activity as low as 1% to 3% is sufficient to rescue the lethal phenotype.	48-50
	Death caused by hemorrhage in neonates, no survival beyond 20 d, no vascular defects.
Factor XI	Mice homozygous for a knockout allele show a tendency for slightly prolonged tail transection bleeding times and are protected from vessel-occluding fibrin formation after transient ischemic brain injury (http://www.informatics.jax.org/).	51,52
Factor XIII-A	No embryonic lethality.
	Compatible with survival to adulthood. However, the survival rate of Fxiii-A KO males at 10 mo was markedly lower than that of the wild-type males. In dead mice, intrathoracic hemorrhage and large hematoma were found. The survival rate of Fxiii-A KO females did not differ.	53-55
	Heart severe fibrosis together with hemosiderin deposition in Fxiii-A KO males.
	Normal embryonic, all homozygous KO mice appeared normal at birth, about half of the pregnant KO females died due to excessive vaginal bleeding.
Factor XIII-B	Significantly reduced level of FXIII A subunit in plasma.
	Prolonged bleeding time.	55,56
	Compatible with survival to adulthood.
	No Fxiii-B KO female mice died during pregnancy, and these animals were capable of successfully carrying multiple litters.
	A low degree of fibrosis in the myocardium was also seen in Fxiii-B KO males.

E, embryonic day.