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 no t known, although in vitro studies indicate that hepsin plays a role i n the initiation of blood coagulation and in hepatocyte growth. To det ermine the functional importance of hepsin, we generated hepsin-defici ent mice by homologous recombination. Homozygous hepsin mice were viab le and fertile, and grew normally. In functional assays including tail bleeding time, plasma dotting times, and tissue factor-or LPS-induced disseminated intravascular coagulation models, no significant differe nce was found between hepsin(-/-) and wild-type litter mates. Liver we ight and serum concentrations of liver-derived proteins or enzymes wer e similar in hepsin(-/-) and wild-type mice. Interestingly, serum conc entrations of bone-derived alkaline phosphatase were approximately two fold 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 indicat e that hepsin is not essential for embryonic development and normal he mostasis. Hepsin(-/-) mice will help to evaluate the long-term effects of hepsin deficiency in these animals.