Kwee L, Burns D K, Rumberger J M, Norton C, Wolitzky B, Terry R, Lombard-Gillooly K M, Shuster D J, Kontgen F, Stewart C
Roche Research Center, Department of Biotechnology, Hoffman-La Roche Inc., Nutley, NJ 07110-1199, USA.
Ciba Found Symp. 1995;189:17-28; discussion 28-34, 77-8. doi: 10.1002/9780470514719.ch3.
A variety of adhesion molecules have been identified which mediate the interaction of leukocytes with endothelial cells. In order to define the role of individual molecules in inflammation we have produced lines of mice which are deficient in the synthesis of specific adhesion molecules. Null mutations were introduced into the genes encoding E-selectin or vascular cell adhesion molecule-1 (VCAM-1) in embryonic stem cells and these cells were used to produce lines of mice carrying the mutation. E-selectin-deficient mice were viable and exhibited no developmental defects. The roles of E- and P-selectin in the influx of neutrophils were examined using these mice. The data suggest that the two selectins are functionally redundant in mediating neutrophil emigration in a model of chemically induced peritonitis. VCAM-1-deficient mice are not viable. Analysis of VCAM-1 gene expression in wild-type embryos and phenotypic analysis of VCAM-1 -/- embryos suggests that VCAM-1 is required for development of the extraembryonic circulatory system and the embryonic heart.
现已鉴定出多种介导白细胞与内皮细胞相互作用的黏附分子。为了确定单个分子在炎症中的作用，我们培育出了特定黏附分子合成缺陷的小鼠品系。在胚胎干细胞中，将无效突变引入编码E-选择素或血管细胞黏附分子-1（VCAM-1）的基因中，并用这些细胞培育出携带该突变的小鼠品系。E-选择素缺陷小鼠能够存活，且未表现出发育缺陷。利用这些小鼠研究了E-选择素和P-选择素在中性粒细胞流入中的作用。数据表明，在化学诱导性腹膜炎模型中，这两种选择素在介导中性粒细胞迁移方面功能冗余。VCAM-1缺陷小鼠无法存活。对野生型胚胎中VCAM-1基因表达的分析以及对VCAM-1 -/-胚胎的表型分析表明，VCAM-1是胚外循环系统和胚胎心脏发育所必需的。
