Effects of targeted disruption of imprinted fetal growth factor genes on maternal glucose metabolism and blood pressure.

我们的目标是测试怀孕期间血糖浓度和血压升高的可能性，这是由于母亲试图限制未出生婴儿大小的基因与婴儿试图促进其生长以增加其生存机会的基因之间的冲突造成的。我们预测，婴儿的基因是通过改变母亲对胰岛素和葡萄糖的反应以及她的血压来做到这一点的。我们计划在两种小鼠模型中直接测试这一点（因为不可能在人类身上这样做）：(1)由于胎盘胰岛素样生长因子2 （IGF2）基因的去除，幼崽出生时很小；(2)由于去除H19基因，幼崽出生时很大，而H19基因通常会降低IGF2的活性。我们计划准确测量胰岛素在体内的工作情况，身体对携带这些基因变化后代的怀孕小鼠的葡萄糖负荷和血压的反应，然后将这些与正常对照的测量结果进行比较。这些实验应该提供关于妊娠期糖尿病和高血压的潜在原因的重要信息。

We aim to test the possibility that rises in blood glucose concentrations and blood pressure in pregnancy result from the conflict between the mother’s genes trying to restrict the size of her unborn baby and the baby’s genes trying to boost its growth in an effort to increase its chance of survival. We predict that the baby’s genes do this by causing alterations in how well their mothers respond to insulin and glucose and in her blood pressure. We plan to test this directly in two mouse models (as it is not possible to do this in humans): (1) where pups are born small due to the removal of the placental insulin-like growth factor 2 (IGF2) gene, (2) where pups are born large due to the removal of the H19 gene which usually reduces IGF2’s activity. We plan to accurately measure how well insulin is working in the body, how the body responds to a glucose load and the blood pressure in pregnant mice carrying offspring with these genetic changes and then compare these to measurements from normal controls. These experiments should provide important information about potential causes of gestational diabetes and high blood pressure.