Mice deficient in hepsin, a serine protease, exhibit normal embryogenesis and unchanged hepatocyte regeneration ability

Hepsin, a liver-enriched novel serine protease, has been implicated in part icipating with normal cell growth, embryogenesis, and blood coagulation pat hway. To study its function in vivo, we have disrupted the mouse hepsin gen e by homologous recombination. Targeted disruption of the hepsin gene and a blation of hepsin message were demonstrated by Southern blotting, Northern blotting and RT-PCR analysis. Homozygous hepsin -/- mice were viable, ferti le, and exhibited no gross abnormalities, as judged by the size, weight and blood coagulation (PT) assays. However, the serum concentration of the bon e form of alkaline phosphatase, aspartate aminotransferase, and alanine ami notransferase of the hepsin -/- mice was mildly elevated, in spire of no ob vious pathological change of hepatocytes, To examine whether hepsin is invo lved in controlling cell growth in adult tissues, 70% hepatectomy was appli ed to the hepsin -/- mice. Liver regeneration proceeded normally in the hep sin -/- mice as judged by the liver mass restoration rate. These results su ggest that loss of hepsin function causes no effect in cell growth and embr yogenesis in vivo, which is in contradiction to the studies using in vitro cell culturing system. Moreover, gross mass regeneration of liver after dam age proceeds normally in the absence of functional hepsin.