In vivo function of versican : Analysis of knockin mice

多功能蛋白聚糖的体内功能：敲入小鼠的分析

基本信息

批准号：
17590361
负责人：
WATANABE Hideto
金额：
$ 2.3万
依托单位：
Aichi Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590361/
关键词：
versican PG-M proteoglycan extracellular matrix collagen TGFbeta BMP コラーゲン線維

项目摘要

We generated knockin mice whose versican lacks the A subdomain of the N-terminal G1 domain. The homozygotes expressed approximately 50% of the mutant versican with decreased incorporation in the extracellular matrix, and showed cardiac dilatation at E9.5 and died by E18.5. In contrast to the complete knockout mice of versican exhibiting severe cardiac malformation, the basic structure of the heart was formed in the kockin homozygotes. Analysis of the heart revealed impaired myocardial cell differentiation with downregulated BMP-signaling, and fibrosis of myocardial wall with up-regulated TGFbeta signaling (submitted).We investigated the role of versican in mesenchymal condensation of the cartilage primodium, using a chondrogenic cell line N1511, and found that chondroitin sulfate (CS) chains of versican facilitate chondrocyte differentiation (Kiamiya, N., et al., J Biol Chem, 2006).We analyzed versican present in the articular cartilage, and found that it is in the form of the proteoglycan aggregate with link protein and hyaluronan. CS of versican was much less sulfated than that of aggrecan (Matsumoto, K., et al., J Biol Chem, 2006).To date, six glycosyltransferases are known to be involved in CS biosynthesis. We attempted to determine the enzyme critical for CS synthesis in cartilage, and found that CS N-acetylgalactosaminyltransferase-1 plays a critical role in the synthesis (Sakai, K., et al., J Biol Chem, 2007).

我们产生了敲击蛋白小鼠，其versican缺乏N末端G1结构域的A子域。纯合子表示大约50％的突变体versican，在细胞外基质中掺入降低，并在E9.5时显示心脏扩张，并在E18.5死亡。与表现出严重心脏畸形的完整敲除小鼠相反，心脏的基本结构在Kockin纯合子中形成。对心脏的分析显示，心肌细胞分化受损，下调BMP信号，以及带有上调的TGFBETA信号传导的心肌壁的纤维化（提交）。我们研究了versican在使用软骨细胞系N1511的骨骼原始骨骼中的间质冷凝物中的作用，并发现五剂量的硫酸软骨素（CS）链有助于软骨细胞分化（Kiamiya，N。，等，J Biol Chem，J Biol Chem，2006年）。蛋白聚糖蛋白质和透明质酸的蛋白聚糖聚集体。 versican的cs硫磺的硫酸含量要比Aggrecan少得多（Matsumoto，K。等，J Biol Chem，2006年。我们试图确定对软骨中CS合成至关重要的酶，并发现CS N-乙酰乳糖酰二氨基转移酶-1在合成中起着至关重要的作用（Sakai，K。等，J Biol Chem，J Biol Chem，2007年）。