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Murine cathepsin F deficiency causes neuronal lipofuscinosis and late-onset neurological disease.
- Source :
-
Molecular and cellular biology [Mol Cell Biol] 2006 Mar; Vol. 26 (6), pp. 2309-16. - Publication Year :
- 2006
-
Abstract
- Cathepsin F (cat F) is a widely expressed lysosomal cysteine protease whose in vivo role is unknown. To address this issue, mice deficient in cat F were generated via homologous recombination. Although cat F-/- mice appeared healthy and reproduced normally, they developed progressive hind leg weakness and decline in motor coordination at 12 to 16 months of age, followed by significant weight loss and death within 6 months. cat F was found to be expressed throughout the central nervous system (CNS). cat F-/- neurons accumulated eosinophilic granules that had features typical of lysosomal lipofuscin by electron microscopy. Large amounts of autofluorescent lipofuscin, characteristic of the neurodegenerative disease neuronal ceroid lipofuscinosis (NCL), accumulated throughout the CNS but not in visceral organs, beginning as early as 6 weeks of age. Pronounced gliosis, an indicator of neuronal stress and neurodegeneration, was also apparent in older cat F-/- mice. cat F is the only cysteine cathepsin whose inactivation alone causes a lysosomal storage defect and progressive neurological features in mice. The late onset suggests that this gene may be a candidate for adult-onset NCL.
- Subjects :
- Age Factors
Age of Onset
Animals
Cathepsin F
Cathepsins genetics
Cathepsins metabolism
Central Nervous System metabolism
Central Nervous System pathology
Lipofuscin metabolism
Mice
Mice, Mutant Strains
Motor Neurons pathology
Motor Neurons ultrastructure
Neuromuscular Diseases etiology
Neuronal Ceroid-Lipofuscinoses epidemiology
Neuronal Ceroid-Lipofuscinoses pathology
Neurons pathology
Sequence Analysis, DNA
Spinal Cord pathology
Spinal Cord ultrastructure
Weight Loss
Cathepsins deficiency
Nervous System Diseases etiology
Neuronal Ceroid-Lipofuscinoses etiology
Subjects
Details
- Language :
- English
- ISSN :
- 0270-7306
- Volume :
- 26
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Molecular and cellular biology
- Publication Type :
- Academic Journal
- Accession number :
- 16508006
- Full Text :
- https://doi.org/10.1128/MCB.26.6.2309-2316.2006