TY - JOUR
T1 - Avoidance of transient cardiomyopathy in cardiomyocyte-targeted tamoxifen-induced MerCreMer gene deletion models
AU - Koitabashi, Norimichi
AU - Bedja, Djahida
AU - Zaiman, Ari L.
AU - Pinto, Yigal M.
AU - Zhang, Manling
AU - Gabrielson, Kathleen L.
AU - Takimoto, Eiki
AU - Kass, David A.
PY - 2009
Y1 - 2009
N2 - Cardiac myocyte targeted MerCreMer transgenic mice expressing tamoxifen-inducible Cre driven by the alpha-myosin heavy chain promoter are increasingly used to control gene expression in the adult heart. Here, we show tamoxifen-mediated MerCreMer (MCM) nuclear translocation can induce severe transient dilated cardiomyopathy in mice with or without loxP transgenes. The cardiomyopathy is accompanied by marked reduction of energy/metabolism and calcium-handling gene expression (eg, PGC1-alpha, peroxisome proliferator-activated alpha, SERCA2A), all fully normalized with recovery. MCM-negative/flox-positive controls display no dysfunction with tamoxifen. Nuclear Cre translocation and equally effective gene knockdown without cardiomyopathy is achievable with raloxifene, suggesting toxicity is not simply from Cre. Careful attention to controls, reduced tamoxifen dosing and/or use of raloxifene is advised with this model
AB - Cardiac myocyte targeted MerCreMer transgenic mice expressing tamoxifen-inducible Cre driven by the alpha-myosin heavy chain promoter are increasingly used to control gene expression in the adult heart. Here, we show tamoxifen-mediated MerCreMer (MCM) nuclear translocation can induce severe transient dilated cardiomyopathy in mice with or without loxP transgenes. The cardiomyopathy is accompanied by marked reduction of energy/metabolism and calcium-handling gene expression (eg, PGC1-alpha, peroxisome proliferator-activated alpha, SERCA2A), all fully normalized with recovery. MCM-negative/flox-positive controls display no dysfunction with tamoxifen. Nuclear Cre translocation and equally effective gene knockdown without cardiomyopathy is achievable with raloxifene, suggesting toxicity is not simply from Cre. Careful attention to controls, reduced tamoxifen dosing and/or use of raloxifene is advised with this model
U2 - https://doi.org/10.1161/CIRCRESAHA.109.198416
DO - https://doi.org/10.1161/CIRCRESAHA.109.198416
M3 - Editorial
C2 - 19520971
SN - 0009-7330
VL - 105
SP - 12
EP - 15
JO - Circulation Research
JF - Circulation Research
IS - 1
ER -