Role of calcium signaling on the hepatic and pancreatic stem cells in the animal model of metabolic syndrome during childhood.

钙网蛋白（CRT）是一种内质网Ca2+结合蛋白，对心脏发育至关重要。α-肌球蛋白重链启动子对钙调蛋白的心脏特异性过表达可导致转基因小鼠完全心脏传导阻滞和猝死。为了进一步研究钙网蛋白的作用机制，我们利用cre-loxP系统构建钙网蛋白时空过表达转基因小鼠。这些小鼠与Nkx2.5- cre小鼠杂交，后者表达受Nkx2.5启动子控制的cre重组酶，Nkx2.5启动子是早期心脏发育所必需的转录因子。钙调钙蛋白过表达与6周龄至10周龄PR间期和QRS间期延长、心动过缓、猝死有关。此外，一些NKx2.5-CRT转基因小鼠在7周龄时出现明显的水肿。综上所述，钙调蛋白在心脏中过表达与HCN1表达降低相关，钙调蛋白在HCN1基因调控中起重要作用。

Calreticulin(CRT) is a Ca2+-binding protein of the endoplasmic reticulum and essential for cardiac development. Cardiac-specific overexpression of calreticulin by α-myosin heavy chain promoter results in complete heart block and sudden death in transgenic mice. Here, to investigate further mechanism of calreticulin, we generate transgenic mice that cause temporal and spatial overexpression of calreticulin using cre-loxP system. The mice were cross-bred with Nkx2.5-Cre mice which express cre recombinase under control of Nkx2.5 promoter, a transcription factor essential for early cardiac development. Overexpression of calreticulin was associated with PR interval and QRS interval prolongation, bradycardia, sudden death between 6-week-old and 10-week-old. Furthermore, some of the NKx2.5-CRT transgenic mice revealed marked edema in 7-week-old. In conclusion, overexpression calreticulin in the heart is associated with a decrease in HCN1 expression and calreticulin plays an important role of HCN1 gene regulation.