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首页> 外文期刊>PLoS Biology >Developmental Programming Mediated by Complementary Roles of Imprinted Grb10 in Mother and Pup
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Developmental Programming Mediated by Complementary Roles of Imprinted Grb10 in Mother and Pup

机译：印迹的Grb10在母性和幼犬中的互补作用介导的发展性程序设计。

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Developmental programming links growth in early life with health status in adulthood. Although environmental factors such as maternal diet can influence the growth and adult health status of offspring, the genetic influences on this process are poorly understood. Using the mouse as a model, we identify the imprinted gene Grb10 as a mediator of nutrient supply and demand in the postnatal period. The combined actions of Grb10 expressed in the mother, controlling supply, and Grb10 expressed in the offspring, controlling demand, jointly regulate offspring growth. Furthermore, Grb10 determines the proportions of lean and fat tissue during development, thereby influencing energy homeostasis in the adult. Most strikingly, we show that the development of normal lean/fat proportions depends on the combined effects of Grb10 expressed in the mother, which has the greater effect on offspring adiposity, and Grb10 expressed in the offspring, which influences lean mass. These distinct functions of Grb10 in mother and pup act complementarily, which is consistent with a coadaptation model of imprinting evolution, a model predicted but for which there is limited experimental evidence. In addition, our findings identify Grb10 as a key genetic component of developmental programming, and highlight the need for a better understanding of mother-offspring interactions at the genetic level in predicting adult disease risk.
机译：发展性编程将早年的成长与成年后的健康状况联系起来。尽管诸如母亲饮食等环境因素会影响后代的生长和成年健康状况，但对该过程的遗传影响却知之甚少。以小鼠为模型，我们确定了印记的基因Grb10是产后营养供应和需求的介体。母体表达的Grb10（控制供给）和后代表达的Grb10（控制需求）的共同作用共同调节后代的生长。此外，Grb10可确定发育过程中瘦肉和脂肪组织的比例，从而影响成年人的能量稳态。最惊人的是，我们表明正常瘦肉/脂肪比例的发育取决于母亲中表达的Grb10对后代肥胖的影响更大，而在后代中表达的Grb10则影响瘦肉质量。 Grb10在母亲和幼崽中的这些独特功能互补地起作用，这与印迹进化的共适应模型一致，该模型是预测的模型，但实验证据有限。此外，我们的发现确定Grb10是发育程序的关键遗传成分，并强调在预测成人疾病风险时需要在基因水平上更好地了解母子相互作用。

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