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 - Kassz, David A.
N1 - Copyright the Publisher 2009. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.
PY - 2009/7/2
Y1 - 2009/7/2
N2 - Cardiac myocyte targeted MerCreMer transgenic mice expressing tamoxifen-inducible Cre driven by the α-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-α, peroxisome proliferator-activated α, 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 α-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-α, peroxisome proliferator-activated α, 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.
UR - http://www.scopus.com/inward/record.url?scp=67949100572&partnerID=8YFLogxK
U2 - 10.1161/CIRCRESAHA.109.198416
DO - 10.1161/CIRCRESAHA.109.198416
M3 - Article
C2 - 19520971
AN - SCOPUS:67949100572
SN - 0009-7330
VL - 105
SP - 12
EP - 15
JO - Circulation Research
JF - Circulation Research
IS - 1
ER -