Generation and characterization of mice deficient in hepsin, a hepatic transmembrane serine protease

J Clin Invest. 1998 Jan 15;101(2):321-6. doi: 10.1172/JCI1617.

Abstract

Hepsin is a type II transmembrane serine protease highly expressed on the surface of hepatocytes. The physiological function of hepsin is not known, although in vitro studies indicate that hepsin plays a role in the initiation of blood coagulation and in hepatocyte growth. To determine the functional importance of hepsin, we generated hepsin-deficient mice by homologous recombination. Homozygous hepsin-/- mice were viable and fertile, and grew normally. In functional assays including tail bleeding time, plasma clotting times, and tissue factor- or LPS-induced disseminated intravascular coagulation models, no significant difference was found between hepsin-/- and wild-type litter mates. Liver weight and serum concentrations of liver-derived proteins or enzymes were similar in hepsin-/- and wild-type mice. Interestingly, serum concentrations of bone-derived alkaline phosphatase were approximately twofold higher in hepsin-/- mice of both sexes when compared with wild-type litter mates. No obvious abnormalities were found in major organs in hepsin-/- mice in histological examinations. Our results indicate that hepsin is not essential for embryonic development and normal hemostasis. Hepsin-/- mice will help to evaluate the long-term effects of hepsin deficiency in these animals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / blood
  • Animals
  • Gene Targeting
  • Liver / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Serine Endopeptidases / deficiency
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / physiology*
  • Thromboplastin / pharmacology

Substances

  • Thromboplastin
  • Alkaline Phosphatase
  • Serine Endopeptidases
  • hepsin