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  Redundant function of the heparan sulfate 6-O-endosulfatases Sulf1 and Sulf2 during skeletal development

Ratzka, A., Kalus, I., Moser, M., Dierks, T., Mundlos, S., & Vortkamp, A. (2008). Redundant function of the heparan sulfate 6-O-endosulfatases Sulf1 and Sulf2 during skeletal development. Developmental Dynamics, 237(2), 339-353. Retrieved from http://www3.interscience.wiley.com/cgi-bin/fulltext/117891195/PDFSTART.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-8081-7 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-8082-5
Genre: Journal Article
Alternative Title : Dev Dynam

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 Creators:
Ratzka, Andreas1, Author
Kalus, Ina, Author
Moser, Markus1, Author
Dierks, Thomas, Author
Mundlos, Stefan2, Author              
Vortkamp, Andrea3, Author              
Affiliations:
1Max Planck Society, ou_persistent13              
2Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433557              
3Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433554              

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Free keywords: bone • cartilage • chondrocyte differentiation • endochondral ossification • heparan sulfate • mouse • Sulf1 • Sulf2 • sulfatase
 Abstract: Modification of the sulfation pattern of heparan sulfate (HS) during organ development is thought to regulate binding and signal transduction of several growth factors. The secreted sulfatases, Sulf1 and Sulf2, desulfate HS on 6-O-positions extracellularly. We show that both sulfatases are expressed in overlapping patterns during embryonic skeletal development. Analysis of compound mutants of Sulf1 and Sulf2 derived from gene trap insertions and targeted null alleles revealed subtle but distinct skeletal malformations including reduced bone length, premature vertebrae ossification and fusions of sternebrae and tail vertebrae. Molecular analysis of endochondral ossification points to a function of Sulf1 and Sulf2 in delaying the differentiation of endochondral bones. Penetrance and severity of the phenotype increased with reduced numbers of functional alleles indicating redundant functions of both sulfatases. The mild skeletal phenotype of double mutants suggests a role for extracellular modification of 6-O-sulfation in fine-tuning rather than regulating the development of skeletal structures

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Language(s): eng - English
 Dates: 2008-01-21
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Method: -
 Identifiers: eDoc: 411673
URI: http://www3.interscience.wiley.com/cgi-bin/fulltext/117891195/PDFSTART
URI: 10.1002/dvdy.21423
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Title: Developmental Dynamics
  Alternative Title : Dev Dynam
Source Genre: Journal
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Pages: - Volume / Issue: 237 (2) Sequence Number: - Start / End Page: 339 - 353 Identifier: -