Document Detail

Versican/PG-M are essential for ventricular septal formation subsequent to cardiac atrioventricular cushion development.
MedLine Citation:
PMID:  22692047     Owner:  NLM     Status:  Publisher    
Versican/PG-M is a large chondroitin sulfate proteoglycan which forms a proteoglycan/ hyaluronan aggregate in the extracellular matrix. We tried to generate the Vcan knockout mice by a conventional method, which resulted in mutant mice Vcan(Δ3/Δ3) whose Vcan lacks the A subdomain of the G1 domain. The Vcan knockout embryos died during the early development stage due to heart defects, but some Vcan(Δ3/Δ3) embryos survived through to the neonatal period. The hearts in Vcan(Δ3/Δ3) newborn mice showed normal cardiac looping, but had ventricular septal defects. Their atrioventricular canal cushion was much smaller than those of wild type embryos, and the extracellular space for cardiac jelly was narrow. The versican deposition in the Vcan(Δ3/Δ3) atrioventricular canal cushion had decreased, while the hyaluronan deposition was maintained and condensed. In the tip of ventricular septa both versican and hyaluronan had decreased. The cell proliferation based upon the number of Ki67 positive cells had remarkably increased in both the atrioventricular canal cushion and ventricular septa, compared to that of wild type embryos. Vcan(Δ3/Δ3) seemed to have endocardial and mesenchymal mixed characteristics. When the ex vivo explant culture of these regions was performed on the collagen gel, hardly any migration to make sufficient space for the extracellular matrix construction was apparent. Our results suggest that the proteoglycan aggregates are necessary in both the atrioventricular canal cushion and ventricular septa to fuse interventricular septa, and the versican A subdomain plays an essential role for the interventricular septal formation by constituting the proteoglycan aggregates.
Sonoko Hatano; Koji Kimata; Noriko Hiraiwa; Moriaki Kusakabe; Zenzo Isogai; Eijiro Adachi; Tamayuki Shinomura; Hideto Watanabe
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-6-12
Journal Detail:
Title:  Glycobiology     Volume:  -     ISSN:  1460-2423     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-6-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9104124     Medline TA:  Glycobiology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Institute for Molecular Science of Medicine, Aichi Medical University, Nagakute, Aichi 480-1195, Japan.
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