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A transgenic mouse model of the ubiquitin/proteasome system.

Nature biotechnology | Aug 1, 2003

Impairment of the ubiquitin/proteasome system has been proposed to play a role in neurodegenerative disorders such as Alzheimer and Parkinson diseases. Although recent studies confirmed that some disease-related proteins block proteasomal degradation, and despite the existence of excellent animal models of both diseases, in vivo data about the system are lacking. We have developed a model for in vivo analysis of the ubiquitin/proteasome system by generating mouse strains transgenic for a green fluorescent protein (GFP) reporter carrying a constitutively active degradation signal. Administration of proteasome inhibitors to the transgenic animals resulted in a substantial accumulation of GFP in multiple tissues, confirming the in vivo functionality of the reporter. Moreover, accumulation of the reporter was induced in primary neurons by UBB+1, an aberrant ubiquitin found in Alzheimer disease. These transgenic animals provide a tool for monitoring the status of the ubiquitin/proteasome system in physiologic or pathologic conditions.

Pubmed ID: 12872133 RIS Download

Mesh terms: Alzheimer Disease | Animals | Boronic Acids | Cells, Cultured | Cysteine Endopeptidases | Fibroblasts | Leupeptins | Mice | Mice, Inbred C57BL | Mice, Transgenic | Microscopy, Fluorescence | Models, Animal | Multienzyme Complexes | Myocytes, Cardiac | Neurodegenerative Diseases | Neurons | Oligopeptides | Organ Specificity | Parkinson Disease | Proteasome Endopeptidase Complex | Recombinant Fusion Proteins | Tissue Distribution | Ubiquitin

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