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上升的可能性，这是因为母亲试图限制未出生婴儿的大小的基因与婴儿试图促进其生长以增加其存活机会的基因之间的冲突。我们预测，婴儿的基因通过改变他们的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。我们计划直接在两个小鼠模型上进行测试(因为这不可能在人类身上做到这一点)：(1)由于胎盘胰岛素样生长因子2(IGF2)基因的移除，幼崽出生时较小；(2)由于移除H19基因，通常会降低IGF2‘S的活性，因此幼崽出生时较大。我们计划准确测量胰岛素在体内的作用情况，身体对葡萄糖负荷的反应，以及怀上这些基因变化后代的怀孕小鼠的血压，然后将这些测量结果与正常对照组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.