The physiological roles of PAPPA2

我的研究目标是了解在连续性状中潜在的生理和遗传因素，如体型。在之前的工作中，我发现PAPPA2基因对控制小鼠生长的变异具有潜在的重要作用。人们对PAPPA2知之甚少，但一个结构相关的基因Pappa在包括怀孕、骨骼发育、心血管疾病、皮肤愈合和衰老在内的各种过程中都发挥着重要作用。 本研究的目的是加深对PAPPA2的S功能的理解。我以小鼠为模型，最近开发了一种我的实验室独有的资源：条件性PAPPA2基因敲除小鼠。条件性基因敲除是一种可以在某些组织中关闭PAPPA2而不影响其在其他组织中的正常功能的基因敲除。我将回答的具体问题包括： (A)PAPPA2是否有助于生长的种内差异？ 了解DNA变异在整个动物水平上导致变异的途径仍然是生物学中的一个主要挑战。 (B)PAPPA2是否在骨骼生长中起作用？ 根据PAPPA2的生化作用，我预测它对骨生理有重要作用。因此，我将关闭骨骼中的PAPPA2，并测量对骨骼长度和骨密度的影响。 (C)PAPPA2是否在胎盘发育中起作用？ PAPPA2在胎盘中高度表达，最近的研究发现它的表达与人类妊娠并发症有关。我将研究胎盘中关闭PAPPA2是否会影响妊娠结局，如出生体重和早产儿发生率。 这项拟议的工作将确定PAPPA2是否可能对某些医疗条件的诊断有用，就像它的近亲Pappa一样。

The goal of my research is to understand the physiological and genetic factors underlying within-species variation in continuous traits such as body size. In previous work, I identified the PAPPA2 gene as potentially important for controlling variation in growth in mice. Little is known about PAPPA2, but a structurally related gene, PAPPA, is important in a variety of processes including pregnancy, bone development, cardiovascular disease, skin healing and aging. The goal of the proposed work is to improve our understanding of PAPPA2's function. I use mice as a model and have recently developed a resource that is unique to my lab: conditional PAPPA2 knock-out mice. A conditional knock-out is one in which it is possible to switch PAPPA2 off in certain tissues without affecting its normal function in other tissues. The specific questions I will address include: (A) Does PAPPA2 contribute to within-species variation in growth? Understanding the pathways through which variation in DNA leads to variation at the whole-animal level remains a major challenge in Biology. (B) Does PAPPA2 play a role in skeletal growth? Based on the biochemical action of PAPPA2, I predict that it is important for bone physiology. I will therefore switch off PAPPA2 in bone and measure effects on bone length and bone mineral density. (C) Does PAPPA2 play a role in placental development? PAPPA2 is highly expressed in the placenta, and recent studies have linked its expression to pregnancy complications in humans. I will examine whether switching off PAPPA2 in the placenta affects pregnancy outcomes such as birth weight and the incidence of prematurity. The proposed work will determine whether PAPPA2 might be useful for the diagnosis of certain medical conditions, as is the case with its close relative, PAPPA.