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. |