| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
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).
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