Gene targeting in hemostasis. Factor X.

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Blood coagulation Factor X (FX) is a vitamin K-dependent serine protease that plays a central role in blood clotting. Additionally, FX may exert other functions beyond coagulation but the precise role of this protein in these processes and the in vivo relevance remains to be further delineated. The development of gene knockout technology has allowed for a direct means to determine the physiological relevance of various proteins in a number of normal and pathological processes. Mice with a total deficiency of FX have been generated by targeted deletion of all exons encoding the mature FX protein. The genotypic distribution indicated that homozygous deficiency results in partial embryonic lethality at embryonic day (E) 11.5-12.5 with signs of massive bleeding but no histologically evident defects in the vasculature of these embryos or their yolk sac. The majority of those that survive to term die within 5 days, most frequently from intraabdominal bleeding. The remainder die between postnatal day (P)5 and P20 with intraabdominal, subcutaneous, or intracranial bleeding or a combination thereof. These observations underline the importance of FX function in embryonic and postnatal survival and confirm that these mice serve as effective models of the bleeding disorders observed in human FX deficiency. While the early FX-/- lethality impedes investigation of potential morphogenetic functions of FX in vivo, such studies may however become feasible through the availability of mice expressing mutant FX proteins, e.g., EPR-1 binding site mutants, or of mice with conditional FX deficiency.

Original languageEnglish (US)
JournalFrontiers in Bioscience
Volume7
StatePublished - 2002
Externally publishedYes

Fingerprint

Factor X
Gene Targeting
Hemostasis
Genes
Factor X Deficiency
Hemorrhage
Proteins
Yolk Sac
Gene Knockout Techniques
Vitamin K
Serine Proteases
Blood Coagulation
Pathologic Processes
Exons
Embryonic Structures
Binding Sites
Human engineering
Coagulation
Technology
Paramagnetic resonance

Cite this

Gene targeting in hemostasis. Factor X. / Rosen, Elliot.

In: Frontiers in Bioscience, Vol. 7, 2002.

Research output: Contribution to journalArticle

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