TGF-B SUPERFAMILY AND MOUSE DEVELOPMENT

描述：(改编自申请者摘要)成长与分化 因子3/VG-1相关蛋白(GDF-3/VGR-2)、激活素BA和激活素BB 转化生长因子β超家族的成员。本组织的成员 超家族在多种发育过程中发挥着重要作用。 为了帮助表征来自这个基因的蛋白质 ，候选人打算研究GDF-3/VGR-2和VGR-2的功能 激活素使用以下策略： 在本提案的第一阶段，目标是：(1)进一步描述 GDF-3/VGR-2基因通过研究该基因的转录模式， 并确定该基因在物种间的保守性；(2)分析 GDF-3/VGR-2基因在小鼠胚胎发育过程中的表达 并在成年小鼠组织中进行原位杂交；(3)灭活 GDF-3/VGR-2基因在胚胎干细胞中的同源重组。(4) 用激活素BB取代激活素BA成熟区以确定 这些蛋白质在功能上是可以互换的。在这个项目的第二阶段 建议的目的是：(1)继续表征形态， 产生的突变小鼠的组织学和生化特征 在第一阶段；以及(2)杂交携带基因突变的小鼠 GDF-3/VGR-2基因座与其他骨形态发生蛋白缺陷小鼠的关系 和激活素。

DESCRIPTION: (Adapted from applicant's abstract) Growth and differentiation factor 3/Vg-1-related protein (GDF-3/Vgr-2), activin BA and activin BB are members of the transforming growth factor beta superfamily. Members of this superfamily play important roles in a variety of developmental processes. In an effort to aid in the characterization of proteins from this superfamily, the candidate intends to study the functions of GDF-3/Vgr-2 and the activins using the following strategies: In phase I of this proposal the aims are: (1) To further characterize the GDF-3/Vgr-2 gene by studying the pattern of transcription from this gene, and to determine the conservation of this gene among species; (2) To analyze the expression pattern of GDF-3/Vgr-2 mRNA in the developing mouse embryo and in adult mouse tissues by in situ hybridization; (3) To inactivate the GDF-3/Vgr-2 gene by homologous recombination in embryonic stem cells. (4) To substitute the activin BA mature region with activin BB to determine if these proteins are functionally interchangeable. In phase II of this proposal the aims are: (1) To continue to characterize the morphologic, histologic and biochemical characteristics of the mutant mice produced during phase 1; and (2) To crossbreed mice carrying a mutation in the GDF-3/Vgr-2 locus with other mice deficient in bone morphogenetic proteins and activins.