The physiological roles of PAPPA2

PAPPA2的生理作用

• 批准号: 326791-2011
• 负责人: Christians, Julian
• 金额: $ 2.26万
• 依托单位: Simon Fraser University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=571843
• 关键词: physiological; roles; PAPPA2

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.

我的研究目标是了解物种内连续性状（如体型）变异的生理和遗传因素。 在以前的工作中，我发现PAPPA2基因对控制小鼠生长变化具有潜在的重要性。 关于PAPPA2知之甚少，但结构相关的基因PAPPA在各种过程中非常重要，包括怀孕，骨骼发育，心血管疾病，皮肤愈合和衰老。 这项工作的目的是提高我们对PAPPA2功能的理解。 我使用小鼠作为模型，最近开发了一种我实验室独有的资源：条件性PAPPA2敲除小鼠。 条件性基因敲除是其中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是否有助于种内生长变异？ 了解DNA变异导致整个动物水平变异的途径仍然是生物学中的一个重大挑战。 (B)PAPPA2在骨骼生长中发挥作用吗？ 基于PAPPA 2的生化作用，我预测它对骨生理学很重要。 因此，我将关闭骨骼中的PAPPA2，并测量对骨长度和骨矿物质密度的影响。 (C)PAPPA2在胎盘发育中起作用吗？ PAPPA2在胎盘中高度表达，最近的研究将其表达与人类妊娠并发症联系起来。我将研究关闭胎盘中的PAPPA2是否会影响妊娠结局，如出生体重和早产的发生率。 拟议的工作将确定PAPPA2是否可用于诊断某些疾病，就像其近亲PAPPA一样。