A transgenic mouse model of the ubiquitin/proteasome system.
Nat Biotechnol
; 21(8): 897-902, 2003 Aug.
Article
em En
| MEDLINE
| ID: mdl-12872133
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
/
Cisteína Endopeptidases
/
Ubiquitina
/
Miócitos Cardíacos
/
Doença de Alzheimer
/
Fibroblastos
/
Complexos Multienzimáticos
/
Neurônios
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article