Aging is not associated with proteasome impairment in UPS reporter mice

Casey Cook, Jennifer Gass, Judith Dunmore, Jimei Tong, Julie Taylor, Jason Eriksen, Eileen McGowan, Jada Lewis, Jennifer Johnston, Leonard Petrucelli

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Background: Covalent linkage of ubiquitin regulates the function and, ultimately, the degradation of many proteins by the ubiquitin-proteasome system (UPS). Given its essential role in protein regulation, even slight perturbations in UPS activity can substantially impair cellular function. Methodology/Principal Findings: We have generated and characterized a novel transgenic mouse model which expresses a previously described reporter for UPS function. This UPS reporter contains a degron sequence attached to the C-terminus of green fluorescent protein, and is predominantly expressed in neurons throughout the brain of our transgenic model. We then demonstrated that this reporter system is sensitive to UPS inhibition in vivo. Conclusions/Significance: Given the obstacles associated with evaluating proteasomal function in the brain, our mouse model uniquely provides the capability to monitor UPS function in real time in individual neurons of a complex organism. Our novel mouse model now provides a useful resource with which to evaluate the impact of aging, as well as various genetic and/or pharmacological modifiers of neurodegenerative disease(s).

Original languageEnglish (US)
Article numbere5888
JournalPloS one
Issue number6
StatePublished - Jun 11 2009

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General


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