Analysis of cathepsin H-deficient mice and identification of a dense cluster of placenta specific peptidase genes ; Analyse von Cathepsin H-defizienten Mäusen und Identifikation der Dichtecluster von plazentaspezifischen Peptidase-Genen

Cathepsin H deficient mice were generated by gene targeting. After confirmation of cathepsin H gene and activity inhibition by southern-northern-western blot analysis and enzyme assay, the cathepsin H deficient mice were analyzed. The first macroscopic observation didn’t show any alteration. The cathepsin H deficient mice are fertile and grow normally. Also histological studies didn’t show also any pathological sign. However, a light embryonic lethality was observed suggesting a role of the cathepsin H in reproduction. Biological screens revealed a weak rate of triglycerides and also an increase of CD4 T cells to the detriment of CD8 T cells showing respectively a potential role of the cathepsin H in the triglycerides absorption or in the regulation of the thyroid activity and in the process of T-cells maturation. Moreover no compensation of the cathepsin B or L was detected in the cathepsin H deficient mice. The use of the â-galactosidase staining confirmed the important expression and thus specific function of the cathepsin H in the lung. Beside the generation and analysis of the cathepsin H-deficient mice a cluster of placenta-specific cysteine peptidase genes was characterized on mouse chromosome 13. This study allowed further defining the map of placenta-specific cysteine peptidase genes and also allowed the identification, in the same cluster, of pseudogenes and of four genes encoding putative cysteine peptidase inhibitors related to the proregion of C1A peptidases.