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 is proposed to have a fundamental role in embryogenesis, fertility, hematopoiesis, macrophage activation, and tissue repair. To assess the in vivo effects of total loss of HGFL, we generated mice with targeted disruption of the gene resulting in loss of the protein. Disruption of the HGFL gene allowed for normal embryogenesis, and followed a Mendelian pattern of genetic transmission. Mice homozygous for the targeted allele (HGFL-/- mice) are fertile, and grow to adulthood without obvious phenotypic abnormalities in unchallenged animals, except for development of lipid-containing cytoplasmic vacuoles in hepatocytes throughout the liver lobules. These histologic changes are not accompanied by discernible changes in synthetic or excretory hepatic functions. Hematopoiesis appears unaltered, and although macrophage activation is delayed in the absence of HGFL, migration to the peritoneal cavity upon challenge with thioglycollate was similar in HGFL-/- and wild-type mice. Challenged with incision to skin, HGFL-/- mice display normal wound healing. These data demonstrate that HGFL is not essential for embryogenesis, fertility, or wound healing. HGFL-deficient mice will provide a valuable means to assess the role of HGFL in hepatic and systemic responses to inflammatory and infectious stimuli in vivo.
Bezerra
J A
JA
Division of Gastroenterology and Nutrition, Children's Hospital Research Foundation and Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio 45229-3039, USA. jorge.bezerra@chmcc.org
Carrick
T L
TL
Degen
J L
JL
Witte
D
D
Degen
S J
SJ
D000483:Alleles; D000818:Animals; D003092:Colitis / Q000235:genetics / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004622:Embryo, Mammalian / Q000502:physiology*; D005298:Fertility; D015723:Gene Library; D005822:Genetic Vectors; D006133:Growth Substances / Q000235:genetics / Q000502:physiology*; D006410:Hematopoiesis; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000378:metabolism; D051379:Mice; D016254:Mutagenesis, Insertional; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins; D011995:Recombination, Genetic; D013047:Specific Pathogen-Free Organisms; D013864:Thioglycolates / Q000494:pharmacology; D014617:Vacuoles / Q000378:metabolism; D014945:Wound Healing / Q000235:genetics
D006133:Growth Substances; D011518:Proto-Oncogene Proteins; D013864:Thioglycolates; C082332:macrophage stimulating protein; D017228:Hepatocyte Growth Factor