Aging is not associated with proteasome impairment in UPS reporter mice.
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).
Cook
Casey
C
Mayo Clinic, Jacksonville, FL, USA.
Gass
Jennifer
J
Dunmore
Judith
J
Tong
Jimei
J
Taylor
Julie
J
Eriksen
Jason
J
McGowan
Eileen
E
Lewis
Jada
J
Johnston
Jennifer
J
Petrucelli
Leonard
L
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*
D025801:Ubiquitin; D049452:Green Fluorescent Proteins; D046988:Proteasome Endopeptidase Complex