Cre-loxP recombination system is widely used in gene function research to realize specific gene knockout or knockin through DNA editing.TheαMHC-MerCreMer transgenic mouse line can achieve conditional cardiomyocyte-sp...Cre-loxP recombination system is widely used in gene function research to realize specific gene knockout or knockin through DNA editing.TheαMHC-MerCreMer transgenic mouse line can achieve conditional cardiomyocyte-specific gene editing and make itself be of high value in cardiovascular research.However,there is an ongoing controversy on cardiomyopathy caused by unspecific Cre activity or related to tamoxifen overload,and the majority of studies only focused on male mice.Here,we investigated in femaleαMHC-MerCreMer mice the effect of tamoxifen on myocardia at a conventional dose of 20 mg/kg for five consecutive days by intraperitoneal injection.Our results confirmed that the conventional dose of tamoxifen administration effectively knock down myocardial MED1 expression within one week,without any changes in body weight or heart and liver mass after a 2-week washout period.Serological examination showed that tamoxifen did not deteriorate hepatic or renal function.Hematoxylin-eosin and Sirius red staining revealed no difference in the structure or fibrosis deposition in the heart upon tamoxifen treatment.F4/80 immunohistochemistry staining showed no signs of increased macrophage infiltration in myocardia.The results of RT-qPCR also confirmed the histological observations.Furthermore,differences in energy metabolism and inflammatory response were observed in femaleαMHC-MerCreMer mice,and the underlying mechanism still needs to be clarified.展开更多
基金the National Natural Science Foundation of China(No.81273878).
文摘Cre-loxP recombination system is widely used in gene function research to realize specific gene knockout or knockin through DNA editing.TheαMHC-MerCreMer transgenic mouse line can achieve conditional cardiomyocyte-specific gene editing and make itself be of high value in cardiovascular research.However,there is an ongoing controversy on cardiomyopathy caused by unspecific Cre activity or related to tamoxifen overload,and the majority of studies only focused on male mice.Here,we investigated in femaleαMHC-MerCreMer mice the effect of tamoxifen on myocardia at a conventional dose of 20 mg/kg for five consecutive days by intraperitoneal injection.Our results confirmed that the conventional dose of tamoxifen administration effectively knock down myocardial MED1 expression within one week,without any changes in body weight or heart and liver mass after a 2-week washout period.Serological examination showed that tamoxifen did not deteriorate hepatic or renal function.Hematoxylin-eosin and Sirius red staining revealed no difference in the structure or fibrosis deposition in the heart upon tamoxifen treatment.F4/80 immunohistochemistry staining showed no signs of increased macrophage infiltration in myocardia.The results of RT-qPCR also confirmed the histological observations.Furthermore,differences in energy metabolism and inflammatory response were observed in femaleαMHC-MerCreMer mice,and the underlying mechanism still needs to be clarified.
