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A transgenic mouse model of the ubiquitin/proteasome system.

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


  • Lindsten K
  • Menéndez-Benito V
  • Masucci MG
  • Dantuma NP


Nature biotechnology

Publication Data

August 1, 2003

Associated Grants


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