title: Mice deficient for the lysosomal proteinase cathepsin D exhibit progressive atrophy of the intestinal mucosa and profound destruction of lymphoid cells.
abstract: 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.
authors.affiliation: Abt. Biochemie II, Universität Göttingen, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Saftig
authors.forename: M
authors.initials: M
authors.lastname: Hetman
authors.forename: W
authors.initials: W
authors.lastname: Schmahl
authors.forename: K
authors.initials: K
authors.lastname: Weber
authors.forename: L
authors.initials: L
authors.lastname: Heine
authors.forename: H
authors.initials: H
authors.lastname: Mossmann
authors.forename: A
authors.initials: A
authors.lastname: Köster
authors.forename: B
authors.initials: B
authors.lastname: Hess
authors.forename: M
authors.initials: M
authors.lastname: Evers
authors.forename: K
authors.initials: K
authors.lastname: von Figura
mesh_terms: D000818:Animals; D001284:Atrophy; D001402:B-Lymphocytes / Q000473:pathology; D002402:Cathepsin D / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D002678:Chimera; D005347:Fibroblasts / Q000378:metabolism; D018390:Gene Targeting; D007082:Ileum / Q000473:pathology; D007413:Intestinal Mucosa / Q000473:pathology*; D007976:Leupeptins / Q000494:pharmacology; D008247:Lysosomes / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010436:Pepstatins / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000473:pathology*; D013601:T-Lymphocytes / Q000473:pathology; D013950:Thymus Gland / Q000473:pathology*
chemical_list: D007976:Leupeptins; D010436:Pepstatins; D012333:RNA, Messenger; C014195:Streptomyces pepsin inhibitor; D002402:Cathepsin D; C032854:leupeptin; C031375:pepstatin