MICE DEFICIENT FOR THE LYSOSOMAL PROTEINASE CATHEPSIN-D EXHIBIT PROGRESSIVE ATROPHY OF THE INTESTINAL-MUCOSA AND PROFOUND DESTRUCTION OF LYMPHOID-CELLS

被引:371
作者
SAFTIG, P
HETMAN, M
SCHMAHL, W
WEBER, K
HEINE, L
MOSSMANN, H
KOSTER, A
HESS, B
EVERS, M
VONFIGURA, K
PETERS, C
机构
[1] UNIV GOTTINGEN,ZENTRUM BIOCHEM & MOLEK ZELLBIOL,BIOCHEM ABT 2,D-37073 GOTTINGEN,GERMANY
[2] GSF MUNCHEN,INST PATHOL,D-85758 OBERSCHLEISSHEIM,GERMANY
[3] UNIV GOTTINGEN,INST IMMUNGENET,D-37073 GOTTINGEN,GERMANY
[4] MAX PLANCK INST IMMUNBIOL,D-79108 FREIBURG,GERMANY
关键词
CATHEPSIN D; GENE TARGETING; INTESTINAL ATROPHY; LYMPHOID DESTRUCTION; PROTEOLYSIS;
D O I
10.1002/j.1460-2075.1995.tb00029.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
xMice 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.
引用
收藏
页码:3599 / 3608
页数:10
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