Non-invasive optical imaging of muscle pathology in mdx mice using cathepsin caged near-infrared imaging.
OBJECTIVE
To develop a reliable live-animal imaging method for monitoring muscle pathology in mouse models of myopathy.


METHODS
A caged near-infrared Cathepsin B (CTSB) substrate, ProSense 680, is evaluated in the dystrophin deficient mdx mice, a genetic homologue of Duchenne muscular dystrophy via optical imaging.


RESULTS
We show high levels of infrared signal in dystrophic muscle relative to healthy muscle at 24 h post-injection. Imaging for CTSB presence revealed localization to inflammatory infiltrates and regenerating muscle fibers. A time series myotoxin-induced muscle injury experiment showed that CTSB activity and its mRNA levels peaked at the interface between inflammation and myoblast fusion stage of recovery. Prednisone treatment in mdx mice resulted in decreased CTSB activity and increased grip strength in forelimbs and hindlimbs.


CONCLUSIONS
Optical imaging of CTSB activity is an ideal method to sensitively monitor inflammation, regeneration, and response to therapy in myopathic skeletal muscle.
Baudy
Andreas R
AR
Research Center for Genetic Medicine, Children's National Medical Center, Washington DC, USA.|Department of Integrative Systems Biology, George Washington University School of Medicine and Health Sciences, Washington DC, USA.
Sali
Arpana
A
Research Center for Genetic Medicine, Children's National Medical Center, Washington DC, USA.
Jordan
Sarah
S
Research Center for Genetic Medicine, Children's National Medical Center, Washington DC, USA.
Kesari
Akanchha
A
Research Center for Genetic Medicine, Children's National Medical Center, Washington DC, USA.
Johnston
Helen K
HK
Research Center for Genetic Medicine, Children's National Medical Center, Washington DC, USA.|Department of Integrative Systems Biology, George Washington University School of Medicine and Health Sciences, Washington DC, USA.
Hoffman
Eric P
EP
Research Center for Genetic Medicine, Children's National Medical Center, Washington DC, USA.|Department of Integrative Systems Biology, George Washington University School of Medicine and Health Sciences, Washington DC, USA.
Nagaraju
Kanneboyina
K
Research Center for Genetic Medicine, Children's National Medical Center, Washington DC, USA. knagaraju@cnmcresearch.org.|Department of Integrative Systems Biology, George Washington University School of Medicine and Health Sciences, Washington DC, USA. knagaraju@cnmcresearch.org.
D000818:Animals; D002401:Cathepsin B / Q000235:genetics / Q000378:metabolism*; D003952:Diagnostic Imaging / Q000379:methods*; D006614:Hindlimb / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007259:Infrared Rays; D007274:Injections, Intraperitoneal; D051379:Mice; D018101:Mice, Inbred mdx; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009132:Muscles / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D009137:Muscular Dystrophy, Animal / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000473:pathology; D032446:Myoblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D055620:Optical Phenomena; D011241:Prednisone / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects; D013379:Substrate Specificity / Q000187:drug effects; D014118:Toxins, Biological / Q000633:toxicity; D014158:Transcription, Genetic / Q000187:drug effects
D012333:RNA, Messenger; D014118:Toxins, Biological; D002401:Cathepsin B; D011241:Prednisone