Generation and characterization of mice deficient in hepsin, a hepatic transmembrane serine protease.
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.
Wu
Q
Q
Department of Cardiovascular Research, Berlex Biosciences, Richmond, California 94804, USA. Qingyu_Wu@Berlex.com
Yu
D
D
Post
J
J
Halks-Miller
M
M
Sadler
J E
JE
Morser
J
J
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D018390:Gene Targeting; D008099:Liver / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012697:Serine Endopeptidases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013925:Thromboplastin / Q000494:pharmacology
D013925:Thromboplastin; D000469:Alkaline Phosphatase; D012697:Serine Endopeptidases; C055645:hepsin