title: Fatal embryonic bleeding events in mice lacking tissue factor, the cell-associated initiator of blood coagulation.
abstract: Tissue factor (TF) is the cellular receptor for coagulation factor VI/VIIa and is the membrane-bound glycoprotein that is generally viewed as the primary physiological initiator of blood coagulation. To define in greater detail the physiological role of TF in development and hemostasis, the TF gene was disrupted in mice. Mice heterozygous for the inactivated TF allele expressed approximately half the TF activity of wild-type mice but were phenotypically normal. However, homozygous TF-/- pups were never born in crosses between heterozygous mice. Analysis of mid-gestation embryos showed that TF-/- embryos die in utero between days 8.5 and 10.5. TF-/- embryos were morphologically distinct from their TF+/+ and TF+/- littermates after day 9.5 in that they were pale, edematous, and growth retarded. Histological studies showed that early organogenesis was normal. The initial failure in TF-/- embryos appeared to be hemorrhaging, leading to the leakage of embryonic red cells from both extraembryonic and embryonic vessels. These studies indicate that TF plays an indispensable role in establishing and/or maintaining vascular integrity in the developing embryo at a time when embryonic and extraembryonic vasculatures are fusing and blood circulation begins.
authors.affiliation: Division of Developmental Biology, Children's Hospital Research Foundation, Cincinnati, OH 45229, USA.
authors.forename: T H
authors.initials: TH
authors.lastname: Bugge
authors.forename: Q
authors.initials: Q
authors.lastname: Xiao
authors.forename: K W
authors.initials: KW
authors.lastname: Kombrinck
authors.forename: M J
authors.initials: MJ
authors.lastname: Flick
authors.forename: K
authors.initials: K
authors.lastname: Holmbäck
authors.forename: M J
authors.initials: MJ
authors.lastname: Danton
authors.forename: M C
authors.initials: MC
authors.lastname: Colbert
authors.forename: D P
authors.initials: DP
authors.lastname: Witte
authors.forename: K
authors.initials: K
authors.lastname: Fujikawa
authors.forename: E W
authors.initials: EW
authors.lastname: Davie
authors.forename: J L
authors.initials: JL
authors.lastname: Degen
mesh_terms: D000818:Animals; D001483:Base Sequence; D001778:Blood Coagulation Disorders / Q000150:complications*; D017931:DNA Primers; D005313:Fetal Death / Q000209:etiology*; D005804:Genes, Lethal; D006470:Hemorrhage; D006579:Heterozygote; D006720:Homozygote; D051379:Mice; D008969:Molecular Sequence Data; D010641:Phenotype; D013925:Thromboplastin / Q000172:deficiency* / Q000235:genetics
chemical_list: D017931:DNA Primers; D013925:Thromboplastin