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Neuronal loss and brain atrophy in mice lacking cathepsins B and L.

ABSTRACT: Cathepsins B and L are widely expressed cysteine proteases implicated in both intracellular proteolysis and extracellular matrix remodeling. However, specific roles remain to be validated in vivo. Here we show that combined deficiency of cathepsins B and L in mice is lethal during the second to fourth week of life. Cathepsin B(-/-)/L(-/-) mice reveal a degree of brain atrophy not previously seen in mice. This is because of massive apoptosis of select neurons in the cerebral cortex and the cerebellar Purkinje and granule cell layers. Neurodegeneration is accompanied by pronounced reactive astrocytosis and is preceded by an accumulation of ultrastructurally and biochemically unique lysosomal bodies in large cortical neurons and by axonal enlargements. Our data demonstrate a pivotal role for cathepsins B and L in maintenance of the central nervous system.

SUBMITTER: Felbor U

PROVIDER: S-EPMC122989 | biostudies-literature | 2002 Jun

REPOSITORIES: biostudies-literature

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Neuronal loss and brain atrophy in mice lacking cathepsins B and L.

Felbor Ute U Kessler Benedikt B Mothes Walther W Goebel Hans H HH Ploegh Hidde L HL Bronson Roderick T RT Olsen Bjorn R BR

Proceedings of the National Academy of Sciences of the United States of America 20020604 12

Cathepsins B and L are widely expressed cysteine proteases implicated in both intracellular proteolysis and extracellular matrix remodeling. However, specific roles remain to be validated in vivo. Here we show that combined deficiency of cathepsins B and L in mice is lethal during the second to fourth week of life. Cathepsin B(-/-)/L(-/-) mice reveal a degree of brain atrophy not previously seen in mice. This is because of massive apoptosis of select neurons in the cerebral cortex and the cerebe ...[more]

PMID: 12048238

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