BONE MORPHOENETIC PROTEIN 2 & 4 GENE REGULATION IN VIVO

描述(改编自申请者摘要)：骨形态发生 蛋白质(BMP)参与多种发育和 皮肤和头发、心脏、肾脏、生殖的分化过程 组织、神经组织和软骨、骨骼和牙齿的发育。在这 应用，研究人员的主要目标是表征机制 BMP2和BMP4基因的转录是通过什么来调节的 体内的成骨细胞和其他组织，并研究其机制 BMP2影响成骨细胞功能。声明的目标是： 1.扩大已有关于BMP对成骨细胞和软骨母细胞影响的研究 特别是鉴定同源异型盒和其他信使核糖核酸物种 受BMP2调节，可能调节BMP2和BMP4的表达 差异化。 2.研究BMP2和BMP4基因的转录调控。 在体内，他们将使用BMP2或BMP4基因片段的转基因小鼠 从5‘侧翼区域和其他区域连接到细菌 β-半乳糖苷酶(LacZ)和/或荧光素酶(Luc)。骨形态发生蛋白2和4基因 将检查转录控制。利用这些小鼠，基因杂交 可以建立候选突变小鼠来评估基因网络和 与BMP2和BMP4基因的相互作用。 3.利用BMP4启动子的特定区域驱动人BMP4 cDNA 在6.5-8.5DPC胚胎的正常BMP4结构域中直接表达， 调查人员将试图营救BMP4纯合子零突变 表型。新的表型可能会出现，这将使我们深入了解这一角色 BMP4的后续开发中。

DESCRIPTION (Adapted from the Applicant's Abstract): The bone morphogenetic proteins (BMPs) are involved in a variety of developmental and differentiation processes in skin and hair, heart, kidney, reproductive tissues, neural tissues and cartilage, bone and tooth development. In this application, the investigators' major goal is to characterize the mechanisms by which transcription of the BMP2 and BMP4 genes are regulated in osteoblasts and other tissues in vivo and to examine the mechanisms by which BMP2 affects osteoblast function. The stated goals are: 1. To extend prior studies on BMP effects on osteoblasts and chondroblasts and in particular to identify homeobox and other mRNA species which are regulated by BMP2 and which may regulate BMP2 and BMP4 expression during differentiation. 2. To characterize transcriptional regulation of the BMP2 and BMP4 genes in vivo, they will use transgenic mice in which BMP2 or BMP4 gene fragments from the 5' flanking region and other regions are linked to bacterial beta-galactosidase (LacZ) and/or luciferase (LUC). BMP2 and 4 gene transcription control will be examined. Using these mice, genetic crosses to candidate mutant mice can be established to evaluate gene networks and interactions with the BMP2 and BMP4 genes. 3. Using specific regions of the BMP4 promoter driving human BMP4 cDNA that directs expression in the normal BMP4 domains of 6.5-8.5 dpc embryos, the investigators will attempt to rescue the BMP4 homozygous null mutant phenotype. New phenotypes may develop that will give insight into the role of BMP4 later in development.