Yan Jianyun, Sultana Nishat, Zhang Lu, Park David S, Shekhar Akshay, Hu Jun, Bu Lei, Cai Chen-Leng
Department of Developmental and Regenerative Biology, The Black Family Stem Cell Institute, and the Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York.
Leon H. Charney Division of Cardiology, New York University School of Medicine, 522 First Avenue, New York, New York.
Genesis. 2015 Jun;53(6):377-86. doi: 10.1002/dvg.22861. Epub 2015 Jun 13.
Tnnt2, encoding thin-filament sarcomeric protein cardiac troponin T, plays critical roles in heart development and function in mammals. To develop an inducible genetic deletion strategy in myocardial cells, we generated a new Tnnt2:MerCreMer (Tnnt2(MerCreMer/+)) knock-in mouse. Rosa26 reporter lines were used to examine the specificity and efficiency of the inducible Cre recombinase. We found that Cre was specifically and robustly expressed in the cardiomyocytes at embryonic and adult stages following tamoxifen induction. The knock-in allele on Tnnt2 locus does not impact cardiac function. These results suggest that this new Tnnt2(MerCreMer/+) mouse could be applied towards the temporal genetic deletion of genes of interests in cardiomyocytes with Cre-LoxP technology. The Tnnt2(MerCreMer/+) mouse model also provides a useful tool to trace myocardial lineage during development and repair after cardiac injury.
编码细肌丝肌节蛋白心肌肌钙蛋白T的Tnnt2在哺乳动物心脏发育和功能中起关键作用。为了在心肌细胞中开发一种可诱导的基因缺失策略，我们构建了一种新的Tnnt2:MerCreMer（Tnnt2(MerCreMer/+)）基因敲入小鼠。利用Rosa26报告基因系检测诱导型Cre重组酶的特异性和效率。我们发现，在他莫昔芬诱导后，Cre在胚胎期和成年期的心肌细胞中特异性且强烈表达。Tnnt2基因座上的敲入等位基因不影响心脏功能。这些结果表明，这种新的Tnnt2(MerCreMer/+)小鼠可用于通过Cre-LoxP技术在心肌细胞中对感兴趣的基因进行时间性基因缺失。Tnnt2(MerCreMer/+)小鼠模型还为追踪心脏损伤后发育和修复过程中的心肌谱系提供了一个有用的工具。
