Noninvasive imaging of in vivo MuRF1 expression during muscle atrophy.
Numerous human diseases can lead to atrophy of skeletal muscle, and loss of this tissue has been correlated with increased mortality and morbidity rates. Clinically addressing muscle atrophy remains an unmet medical need, and the development of preclinical tools to assist drug discovery and basic research in this effort is important for advancing this goal. In this report, we describe the development of a bioluminescent gene reporter rat, based on the zinc finger nuclease-targeted insertion of a bicistronic luciferase reporter into the 3' untranslated region of a muscle specific E3 ubiquitin ligase gene, MuRF1 (Trim63). In longitudinal studies, we noninvasively assess atrophy-related expression of this reporter in three distinct models of muscle loss (sciatic denervation, hindlimb unloading and dexamethasone-treatment) and show that these animals are capable of generating refined detail on in vivo MuRF1 expression with high temporal and anatomical resolution.
Discovery Research, Rigel Pharmaceuticals Inc., South San Francisco, California, United States of America.
Wei
W
Li
Discovery Research, Rigel Pharmaceuticals Inc., South San Francisco, California, United States of America.
Mark D
MD
Claypool
Discovery Research, Rigel Pharmaceuticals Inc., South San Francisco, California, United States of America.
Annabelle M
AM
Friera
Discovery Research, Rigel Pharmaceuticals Inc., South San Francisco, California, United States of America.
John
J
McLaughlin
Discovery Research, Rigel Pharmaceuticals Inc., South San Francisco, California, United States of America.
Kristen A
KA
Baltgalvis
Discovery Research, Rigel Pharmaceuticals Inc., South San Francisco, California, United States of America.
Ira J
IJ
Smith
Discovery Research, Rigel Pharmaceuticals Inc., South San Francisco, California, United States of America.
Taisei
T
Kinoshita
Discovery Research, Rigel Pharmaceuticals Inc., South San Francisco, California, United States of America.
Kathy
K
White
Discovery Research, Rigel Pharmaceuticals Inc., South San Francisco, California, United States of America.
Wayne
W
Lang
Discovery Research, Rigel Pharmaceuticals Inc., South San Francisco, California, United States of America.
Guillermo
G
Godinez
Discovery Research, Rigel Pharmaceuticals Inc., South San Francisco, California, United States of America.
Donald G
DG
Payan
Discovery Research, Rigel Pharmaceuticals Inc., South San Francisco, California, United States of America.
Todd M
TM
Kinsella
D000818:Animals; D005260:Female; D017930:Genes, Reporter; D019417:Hindlimb Suspension; D008163:Luminescent Measurements / Q000379:methods*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009133:Muscular Atrophy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
D009124:Muscle Proteins; D000070584:Tripartite Motif Proteins; C499086:Trim63 protein, rat; D044767:Ubiquitin-Protein Ligases