BIOLOGICAL EFFECTS OF TARGETED INACTIVATION OF HEPATOCYTE GROWTH FACTOR-LIKE PROTEIN IN MICE

Hepatocyte growth factor-like protein (HGFL) is a liver-derived serum glycoprotein involved in cell proliferation and differentiation, and i s proposed to have a fundamental role in embryogenesis, fertility, hem atopoiesis, macrophage activation, and tissue repair, To assess the in vivo effects of total loss of HGFL, we generated mice with targeted d isruption of the gene resulting in loss of the protein, Disruption of the HGFL gene allowed for normal embryogenesis, and followed a Mendeli an pattern of genetic transmission. Mice homozygous for the targeted a llele (HGFL(-/-) mice) are fertile, and grow to adulthood without obvi ous phenotypic abnormalities in unchallenged animals, except for devel opment of lipid-containing cytoplasmic vacuoles in hepatocytes through out the liver lobules. These histologic changes are not accompanied by discernible changes in synthetic or excretory hepatic functions, Hema topoiesis appears unaltered, and although macrophage activation is del ayed in the absence of HGFL, migration to the peritoneal cavity upon c hallenge with thioglycollate was similar in HGFL(-/-) and wild-type mi ce. Challenged with incision to skin, HGFL(-/-) mice display normal wo und healing, These data demonstrate that HGFL is not essential for emb ryogenesis, fertility, or wound healing, HGFL-deficient mice will prov ide a valuable means to assess the role of HGFL in hepatic and systemi c responses to inflammatory and infectious stimuli in vivo.