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对成人健康产生深远的影响。大多数决定最终体重和功能的事件都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）信号作出反应而产生的。我们提出，这不是全貌和另一个因素？细胞因子刺激因子1 (CSF1) -由免疫细胞巨噬细胞产生，有助于控制GH/IGF-1系统，从而有助于控制出生后生长。我们的数据表明，缺乏CSF1功能的动物与缺乏GH/IGF-1的动物有一系列共同的发育和生长异常，我们基于这一假设。虽然我们的初步数据令人信服，但挑战仍然是了解这些不同因素如何相互作用以控制增长。有了这些知识，我们就能更好地评估克服生长障碍的策略。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。具体来说，我们将确定减少CSF1信号传导对生长的影响，以及提高CSF1水平作为生长受损的可能治疗方法的有益影响。

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.