Towards specific functions of lysosomal cysteine peptidases: phenotypes ofmice deficient for cathepsin B or cathepsin L

The lysosomal cysteine peptidases cathepsin B and cathepsin L are abundant and ubiquitously expressed members of the papain family, and both enzymes c ontribute to the terminal degradation of proteins in the lysosome. However, there is accumulating evidence for specific functions of lysosomal proteas es in health and disease. The generation of 'knock out' mouse strains that are deficient in lysosomal proteases provides a valuable tool for evaluatio n of existing hypotheses and gaining new insights into the in vivo function s of these proteases. In this minireview, we summarise and discuss the find ings obtained by analysis of mice that are devoid of cathepsin B or catheps in L. In brief, cathepsin L appears to be critically involved in epidermal homeostasis, regulation of the hair cycle, and MHC class Ii-mediated antige n presentation in cortical epithelial cells of the thymus. Cathepsin B play s a major role in pathological trypsinogen activation in the early course o f experimental pancreatitis and contributes significantly to TNF-alpha indu ced hepatocyte apoptosis.