Divinations and surprises: genetic analysis of caspase function in mice

Caspases are critical mediators of apoptosis, the principle mechanism by which extra and harmful cells are eliminated to ensure proper development and maintain cellular homeostasis in all multicellular organisms. While compelling evidence suggests that the activation of these otherwise latent intracellular proteases is required for the execution of most, if not all apoptosis in mammals, the presence of more than a dozen caspases presents a major challenge to our understanding of the precise function of individual caspases in vivo. Using a genetic approach, several groups have generated transgenic mice deficient in various caspases so as to investigate their physiological functions. In this review, we will discuss what these studies have revealed about the role of individual caspase in development, apoptosis, and inflammation, with a particular focus on the predictable phenotypes versus the surprises based on in vitro results, as well as the implications of these findings.