title: Synthesis of a mouse model of the dysfibrinogen Vlissingen/Frankfurt IV.
abstract: The dysfibrinogen Vlissingen/Frankfurt IV is characterized as a deletion of Asn319 and Asp320 from the C-terminus of the gamma-chain of fibrinogen. This dysfibrinogen, which was identified in several family members that are all heterozygous for the in-frame 6-bp deletion, is associated with both venous and arterial thrombosis. Here, we describe the generation of a murine model of the V/F IV dysfibrinogen using gene targeting of mouse gamma-chain DNA. Preliminary analysis shows that the human and mouse variant fibrinogens are similar: analogous to the human V/F IV protein, the D1 fragment of the variant mouse fibrinogen is partially protected from digestion in the presence of calcium or Gly-Pro-Arg-Pro. These heterozygous mice provide the first opportunity to examine the association of thrombophilia and dysfibrinogenemia in a controlled genetic background.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599-7525, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Hogan
authors.forename: N
authors.initials: N
authors.lastname: Maeda
authors.forename: K D
authors.initials: KD
authors.lastname: Kluckman
authors.forename: S T
authors.initials: ST
authors.lastname: Lord
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D015241:Fibrinogens, Abnormal / Q000737:chemistry / Q000235:genetics*; D005822:Genetic Vectors; D006579:Heterozygote; D006801:Humans; D008297:Male; D051379:Mice; D017386:Sequence Homology, Amino Acid
chemical_list: D017931:DNA Primers; D015241:Fibrinogens, Abnormal