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Mice deficient for the lysosomal proteinase cathepsin D exhibit progressive atrophy of the intestinal mucosa and profound destruction of lymphoid cells.
Author(s) -
Saftig P.,
Hetman M.,
Schmahl W.,
Weber K.,
Heine L.,
Mossmann H.,
Köster A.,
Hess B.,
Evers M.,
Figura K.
Publication year - 1995
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1995.tb00029.x
Subject(s) - biology , proteolysis , cathepsin d , phenocopy , calpain , cathepsin , intestinal mucosa , atrophy , cathepsin c , cathepsin b , homeostasis , microbiology and biotechnology , medicine , biochemistry , enzyme , gene , genetics , mutant
Mice deficient for the major lysosomal aspartic proteinase cathepsin D, generated by gene targeting, develop normally during the first 2 weeks, stop thriving in the third week and die in a state of anorexia at day 26 +/− 1. An atrophy of the ileal mucosa first observed in the third week progresses towards widespread intestinal necroses accompanied by thromboemboli. Thymus and spleen undergo massive destruction with fulminant loss of T and B cells. Lysosomal bulk proteolysis is maintained. These results suggest, that vital functions of cathepsin D are exerted by limited proteolysis of proteins regulating cell growth and/or tissue homeostasis, while its contribution to bulk proteolysis in lysosomes appears to be non‐critical.