Regulation and Functional Analysis of Type X Collagen

X型胶原蛋白的调控及功能分析

• 批准号: 6786526
• 负责人: Richard R Behringer
• 金额: $ 21.3万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6786526
• 关键词: bone development; bone morphogenetic proteins; cartilage development; cell differentiation; chondrocytes; collagen; connective tissue development; developmental genetics; gene expression; gene targeting; genetic regulatory element; genetic transcription; genetically modified animals; growth factor receptors; laboratory mouse; mammalian embryology; normal ossification; protein structure function; recombinase

Bone morphogenetic proteins (BMP) are members of the transforming growth factor-b (TGF-b) family of cytokines that play a variety of different roles during animal development. Although BMPs were first identified for their bone-inducing abilities, surprisingly there is currently no in vivo evidence for a general requirement for BMP signaling in skeleton formation. Standard mouse knockouts for genes encoding BMP signaling proteins have not been very informative because many die during early embryogenesis before skeleton formation. We have performed conditional genetic studies and provide evidence that BMP type I receptors are essential and act redundantly for skeleton formation, thus revealing BMP signaling complexity. In combination with transgenic mice that express cre recombinase in limb mesenchyme and chondrocytes, we propose to examine the requirement and complexity of BMP signaling proteins in skeletal development.

骨形态发生蛋白（BMP）是转化生长因子-B（TGF-B）的细胞因子家族的成员，它们在动物发育过程中起多种不同作用。尽管BMP最初是因为其骨骼诱导能力而被鉴定出来的，但令人惊讶的是，目前尚无体内证据表明骨骼形成中BMP信号的一般要求。编码BMP信号蛋白的基因的标准小鼠基因敲除并不是很有信息，因为许多在骨骼形成之前的早期胚胎发生过程中死亡。我们已经进行了条件遗传研究，并提供了证据表明BMP I型受体至关重要，并且对骨架的形成起作用，从而揭示了BMP信号传导的复杂性。结合在肢体间充质和软骨细胞中表达CRE重组酶的转基因小鼠， 我们建议检查BMP信号蛋白在骨骼发育中的需求和复杂性。