Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.
Skip to main content

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.

Original publication

DOI

10.1073/pnas.112632299

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

11/06/2002

Volume

99

Pages

7883 - 7888

Keywords

Animals, Apoptosis, Atrophy, Brain, Cathepsin B, Cathepsin L, Cathepsins, Cerebellum, Cysteine Endopeptidases, Endosomes, Genotype, Lysosomes, Mice, Mice, Knockout, Neurons