title: Aging is not associated with proteasome impairment in UPS reporter mice.
abstract: 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.
  
  
  RESULTS
  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
  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).
authors.affiliation: Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Casey
authors.initials: C
authors.lastname: Cook
authors.forename: Jennifer
authors.initials: J
authors.lastname: Gass
authors.forename: Judith
authors.initials: J
authors.lastname: Dunmore
authors.forename: Jimei
authors.initials: J
authors.lastname: Tong
authors.forename: Julie
authors.initials: J
authors.lastname: Taylor
authors.forename: Jason
authors.initials: J
authors.lastname: Eriksen
authors.forename: Eileen
authors.initials: E
authors.lastname: McGowan
authors.forename: Jada
authors.initials: J
authors.lastname: Lewis
authors.forename: Jennifer
authors.initials: J
authors.lastname: Johnston
authors.forename: Leonard
authors.initials: L
authors.lastname: Petrucelli
mesh_terms: D000375:Aging; D000818:Animals; D005260:Female; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019636:Neurodegenerative Diseases / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000235:genetics* / Q000502:physiology*; D017434:Protein Structure, Tertiary; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025801:Ubiquitin / Q000235:genetics* / Q000502:physiology*
chemical_list: D025801:Ubiquitin; D049452:Green Fluorescent Proteins; D046988:Proteasome Endopeptidase Complex