CSF1 and the control of postnatal growth and organ development in the rat

在怀孕期间，身体的许多主要器官获得了子宫外生命所必需的许多功能。在这些生命早期阶段对生长的影响可能会对成年人的健康产生深远的影响。决定最终体重和功能的大多数事件是由血液中循环的蛋白质控制的。这种因子被称为胰岛素生长因子-1(IGF1)。传统知识表明，这种因子是在肝脏中对生长激素(GH)信号做出反应的。我们提出，这不是全貌和另一个因素？被称为巨噬细胞的免疫细胞产生的细胞因子刺激因子1(CSF1)有助于控制GH/IGF-1系统，从而有助于控制出生后的生长。我们的假设基于我们的数据，表明缺乏CSF1功能的动物与GH/IGF-1缺乏的动物有一系列共同的发育和生长异常。尽管我们的初步数据令人信服，但挑战仍然是理解这些不同因素是如何相互作用来控制增长的。有了这些知识，我们将能够更好地评估克服增长障碍的战略。为了实现这些目标，我们的目标是在大鼠身上开发新的转基因技术。具体地说，我们将确定减少CSF1信号对生长的影响以及提高CSF1水平作为对生长受损的可能治疗的有益影响。

During pregnancy, many major organs of the body gain the many functions that will be necessary for life outside of the womb. Effects on growth at these early stages of life can have profound consequences for adult health. Most of the events that determine final body mass and function are controlled by protein found circulating in blood. This factor is called Insulin Growth Factor-1 (IGF1). Traditional knowledge indicates that this factor is made in the liver in response to growth hormone (GH) signals. We propose that this is not the entire picture and another factor ? Cytokine Stimulating Factor 1 (CSF1) - produced by the immune cells called macrophages contribute to the control the GH/IGF-1 system and thus contribute to the control of postnatal growth. We base this hypothesis on our data indicating that animals which lack CSF1 function have a range of developmental and growth abnormalities in common to animals deficient in GH/IGF-1. Although our preliminary data is compelling, the challenge remains to understand how these various factors interact to control growth. With this knowledge we will be better able to evaluate strategies to overcome growth impairment. To address these goals we aim to exploit new transgenic technologies in the rat. Specifically we will determine the consequence of reducing CSF1 signalling on growth and beneficial effects of elevating CSF1 levels as a possible treatment of impaired growth.