Human genetic diseases have provided valuable information about vascular physiology and pathology. Well known examples in the specific area of cell adhesion include the insights into platelet function arising from analyses of Glanzmann’s thrombasthenia and von Willebrand’s disease and into leukocyte function from studies of the leukocyte adhesion deficiency (LAD) syndromes. Invaluable further information could be gleaned from additional mutations and from combinations of mutations. With the advent of genomic analysis, we can anticipate the discovery and isolation of many other such “disease genes,” including those contributing to multigenic traits. However, human mutations obviously cannot be obtained or recombined at will and only those compatible with viability can be at all readily studied. What is needed is a system for exploiting both the wealth of new genetic information and our rapidly deepening understanding of the molecular and cellular bases for cell adhesion, allowing ready generation and manipulation of mutations in the genes for adhesion proteins. Such genetic engineering would allow detailed analyses of the roles of adhesion proteins in normal vascular processes and their involvement in various diseases. Fortunately, such a system now exists and the mouse is it.

Recent developments in molecular genetic analyses of mice make it possible to generate null mutations in any gene of interest; that is now routine and much useful information has already been obtained from such “knockout” mice. Transgenic mice, to which genes have been added, have been available for longer and provide another way of manipulating the genome of mice. Furthermore, it is now becoming possible to generate subtle mutations and tissue-specific or regulatable expression or ablation of specific genes (1, 2). Mice can be readily interbred to combine mutations in multiple genes, providing animal models for multigenic defects. In this brief article, we will consider some of the insights already obtained from studies of mice with mutations in genes for vascular adhesion molecules and, more importantly, will consider the rich possibilities they offer for future understanding of human physiology and disease.