DOWN-REGUL OF BONE MORPHOG PROTEIN-11 BY ITS PROPEPTIDE DURING EMBRYONIC DEV

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 骨形态发生蛋白11（BMP-11或GDF-11）与人骨形成蛋白11（BMP-11）的氨基酸序列有90%的同源性， 与肌生长抑制素或GDF-8的序列。BMP-11基因敲除小鼠引起了戏剧性的转变 脊椎和新生儿的死亡。此外，它可能像肌肉生长抑制素一样调节肌肉质量。 然而，BMP-11在胚胎期骨骼形成调控中的特殊作用， 和胎儿阶段还没有很好的定义。根据我们之前的证据， 肌生成抑制素前肽的表达显著抑制肌生成抑制素功能， 肌肉质量，我们产生了转基因小鼠，过度表达BMP-11前肽下， 成骨细胞特异性启动子的控制。活的动物出生时， 脊椎到胸椎这种BMP-11前肽小鼠模型提供了一种重要的 用于研究BMP-11在肌肉骨骼形成和发育中的作用的动物模型。 本试验项目旨在表征骨形成蛋白-11的骨骼形成和肌生成 前肽转基因小鼠在胚胎期和胎儿期，并进一步研究 BMP-11及其前肽在间充质细胞分化中的作用 成骨细胞和软骨细胞谱系。研究方法将结合 转基因小鼠和具有用于细胞增殖测定的体内BrdU标记的细胞培养物，基因 通过qRT-PCR和Western印迹分析表达。预计该项目将取得成果 揭示胚胎时期控制骨形成的分子和细胞机制 这对于理解骨骼异常和出生缺陷很重要。 这些调节机制的新知识可能有助于开发新的策略， 防止人类出生缺陷。对我们来说，这个项目的直接好处是， 获取并公布用于准备NIH拨款申请的初步数据。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Bone morphogenetic protein 11 (BMP-11 or GDF-11) has 90% identity in amino acid sequences with myostatin or GDF-8. BMP-11 knockout mice caused dramatic transformation of vertebrae and death of newborns. Also, it may act like myostatin to regulate muscle mass. However, the specific roles of BMP-11 in regulation of skeletal formation during embryonic and fetal stages have not been well defined. Based on our previous evidence that transgenic expression of myostatin propeptide significantly depressed myostatin function and increased muscle mass, we generated transgenic mice that over-express BMP-11 propeptide under the control of an osteoblast-specific promoter. Live animals were born with transformed cervical vertebra to a thoracic vertebra. This BMP-11 propetide mouse model offers an important animal model for studying the role of BMP-11 in musculoskeletal formation and development. This pilot project is designed to characterize skeletal formation and myogenesis of BMP-11 propeptide transgenic mice during the embryonic and fetal periods, and further to investigate the role of BMP-11 and its propeptide in the regulation of differentiation of mesenchymal stem cells to osteogenic and chondrogenic lineage. Research methods will incorporate transgenic mice and cell culture with in vivo BrdU labeling for cell proliferation assay, gene expression analysis by qRT-PCR and Western blotting. Results from this project are expected to reveal molecular and cellular mechanisms that control bone formation during embryo development, which is important for understanding skeletal abnormalities and birth defects. The new knowledge of these regulatory mechanisms may help to develop novel strategies for preventing human birth defects. The immediate, direct benefit of this project for us is to obtain and publish the preliminary data for the preparation of a NIH grant application.