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Publication : A mouse model for monitoring calpain activity under physiological and pathological conditions.

First Author  Bartoli M Year  2006
Journal  J Biol Chem Volume  281
Issue  51 Pages  39672-80
PubMed ID  17056592 Mgi Jnum  J:117658
Mgi Id  MGI:3697051 Doi  10.1074/jbc.M608803200
Citation  Bartoli M, et al. (2006) A mouse model for monitoring calpain activity under physiological and pathological conditions. J Biol Chem 281(51):39672-80
abstractText  Calpains are Ca(2+)-dependent cysteine proteases known to be important for the regulation of cell functions and which aberrant activation causes cell death in a number of degenerative disorders. To provide a tool for monitoring the status of calpain activity in vivo under physiological and pathological conditions, we created a mouse model that expresses ubiquitously a fluorescent reporter consisting of eCFP and eYFP separated by a linker cleavable by the ubiquitous calpains. We named this mouse CAFI for calpain activity monitored by FRET imaging. Our validation studies demonstrated that the level of calpain activity correlates with a decrease in FRET (fluorescence resonance energy transfer) between the two fluorescent proteins. Using this model, we observed a small level of activity after denervation and fasting, a high level of activity during muscle regeneration and ischemia, and local activity in damaged myofibers after exercise. Finally, we crossed the CAFI mouse with the alpha-sarcoglycan-deficient model, demonstrating an increase of calpain activity at the steady state. Altogether, our results present evidence that CAFI mice could be a valuable tool in which to follow calpain activity at physiological levels and in disease states.
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