Divinations and surprises: Genetic analysis of caspase function in mice

Caspases are critical mediators of apoptosis, the principle mechanism by wh ich extra and harmful cells are eliminated to ensure proper development and maintain cellular homeostasis in all multicellular organisms. While compel ling evidence suggests that the activation of these otherwise latent intrac ellular proteases is required for the execution of most, if not all apoptos is in mammals, the presence of more than a dozen caspases presents a major challenge to our understanding of the precise function of individual caspas es in vivo. Using a genetic approach, several groups have generated transge nic mice deficient in various caspases so as to investigate their physiolog ical functions. In this review, we will discuss what these studies have rev ealed about the role of individual caspase in development, apoptosis, and i nflammation, with a particular focus on the predicable phenotypes versus th e surprises based on in vitro results, as well as the implications of these findings. (C) 2000 Academic Press.