Bezerra J A, Carrick T L, Degen J L, Witte D, Degen S J
Division of Gastroenterology and Nutrition, Children's Hospital Research Foundation and Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio 45229-3039, USA.
J Clin Invest. 1998 Mar 1;101(5):1175-83. doi: 10.1172/JCI1744.
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.
肝细胞生长因子样蛋白（HGFL）是一种源自肝脏的血清糖蛋白，参与细胞增殖和分化，被认为在胚胎发育、生育能力、造血、巨噬细胞激活和组织修复中发挥着重要作用。为了评估HGFL完全缺失的体内效应，我们构建了基因靶向敲除的小鼠，导致该蛋白缺失。HGFL基因的敲除允许正常的胚胎发育，并遵循孟德尔遗传模式。靶向等位基因纯合的小鼠（HGFL-/-小鼠）具有生育能力，在未受挑战的动物中可生长至成年，无明显表型异常，但整个肝小叶的肝细胞中出现含脂细胞质空泡。这些组织学变化并未伴随肝脏合成或排泄功能的明显改变。造血功能似乎未受影响，尽管在没有HGFL的情况下巨噬细胞激活延迟，但在用巯基乙酸盐攻击后，HGFL-/-小鼠和野生型小鼠向腹腔的迁移相似。在用皮肤切口进行挑战时，HGFL-/-小鼠表现出正常的伤口愈合。这些数据表明，HGFL对于胚胎发育、生育能力或伤口愈合并非必不可少。HGFL缺陷小鼠将为评估HGFL在体内对炎症和感染刺激的肝脏及全身反应中的作用提供有价值的手段。
