BONE MORPHOENETIC PROTEIN 2 & 4 GENE REGULATION IN VIVO

描述（改编自申请人的摘要）：骨形态发生 骨形成蛋白（BMPs）参与多种发育和 皮肤和毛发、心脏、肾脏、生殖系统 组织、神经组织和软骨、骨骼和牙齿发育。 在这 应用程序，研究人员的主要目标是表征机制 BMP 2和BMP 4基因的转录受其调控， 成骨细胞和其他组织在体内，并检查的机制， BMP 2影响成骨细胞功能。 所述目标是： 1. 扩展先前关于BMP对成骨细胞和成软骨细胞作用的研究 特别是鉴定同源框和其他mRNA种类， 它可以调节BMP 2和BMP 4的表达， 分化 2. 为了表征BMP 2和BMP 4基因的转录调控， 在体内，他们将使用转基因小鼠，其中BMP 2或BMP 4基因片段 从5'侧翼区和其他区域连接到细菌 β-半乳糖苷酶（LacZ）和/或萤光素酶（LUC）。 BMP 2和4基因 将检查转录控制。 利用这些老鼠， 可以建立候选突变小鼠来评估基因网络， 与BMP 2和BMP 4基因的相互作用。 3. 使用驱动人BMP 4 cDNA的BMP 4启动子的特定区域， 指导6.5-8.5 dpc胚胎的正常BMP 4结构域的表达， 研究者将尝试挽救BMP 4纯合无效突变体 表型 新的表型可能会发展，这将使人们深入了解的作用， BMP 4在发展中的作用

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.