title: The murine platelet and plasma factor V pools are biosynthetically distinct and sufficient for minimal hemostasis.
abstract: Coagulation factor V (FV) is a central regulator of the coagulation cascade. Circulating FV is found in plasma and within platelet alpha granules. The specific functions of these distinct FV pools are uncertain. We now report the generation of transgenic mice with FV gene expression restricted to either the liver or megakaryocyte/platelet lineage using bacterial artificial chromosome (BAC) constructs. Six of 6 independent albumin BAC transgenes rescue the neonatal lethal hemorrhage of FV deficiency. Rescued mice all exhibit liver-specific Fv expression at levels ranging from 6% to 46% of the endogenous Fv gene, with no detectable FV activity within the platelet pool. One of the 3 Pf4 BAC transgenes available for analysis also rescues the lethal FV null phenotype, with FV activity restricted to only the platelet pool (approximately 3% of the wild-type FV level). FV-null mice rescued by either the albumin or Pf4 BAC exhibit nearly normal tail bleeding times. These results demonstrate that Fv expression in either the platelet or plasma FV pool is sufficient for basal hemostasis. In addition, these findings indicate that the murine platelet and plasma FV pools are biosynthetically distinct, in contrast to a previous report demonstrating a plasma origin for platelet FV in humans.
authors.affiliation: Department of Internal Medicine, Division of Molecular Medicine and Genetics, University of Michigan, Ann Arbor, 48109,USA.
authors.forename: Hongmin
authors.initials: H
authors.lastname: Sun
authors.forename: Tony L
authors.initials: TL
authors.lastname: Yang
authors.forename: Angela
authors.initials: A
authors.lastname: Yang
authors.forename: Xixi
authors.initials: X
authors.lastname: Wang
authors.forename: David
authors.initials: D
authors.lastname: Ginsburg
mesh_terms: D000483:Alleles; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D022202:Chromosomes, Artificial, Bacterial; D003433:Crosses, Genetic; D004926:Escherichia coli / Q000378:metabolism; D005165:Factor V / Q000737:chemistry / Q000502:physiology*; D005838:Genotype; D006487:Hemostasis; D007128:Immunoglobulin Fragments; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D011995:Recombination, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution; D019076:Transgenes
chemical_list: D007128:Immunoglobulin Fragments; D012333:RNA, Messenger; D005165:Factor V