Investigation of the angiogenic programme with tissue-specific and inducible genetic approaches in mice

Blood vessels form a highly organized hierarchical network throughout the vertebrate body, integrate functionally into very different tissue environments and remain remarkably adaptable to changing local requirements. The importance of a correctly formed and functional vascular network is highlighted by numerous human pathologies, which involve defects such as compromised blood circulation, destabilization of vessel walls or deregulated angiogenesis. Genetically modified mice are powerful tools for the functional characterization of genes, and can also serve as models of human diseases. However, targeted inactivation of genes essential for blood vessel morphogenesis is usually incompatible with embryonic survival, so studies in adult mice are precluded. Moreover, mutant phenotypes can be a complex combination of defects in different tissues and cell types. Tissue-specific and inducible genetic approaches allow us to overcome many of these limitations. In particular, it is possible to perform manipulations in a spatially (i.e. cell type-specific) and temporally controlled fashion, which makes possible studies throughout development and in adults. We have generated several transgenic Cre and tamoxifen-induble CreERT2 lines that enable the selective targeting of vascular cell populations. Here, I will discuss the characterization of these lines and present examples of their application in the analysis of vascular development.