Secreted sulfatases Sulf1 and Sulf2 have overlapping yet essential roles in mouse neonatal survival.
<h4>Background</h4>Heparan sulfate proteoglycans (HSPGs) use highly sulfated polysaccharide side-chains to interact with several key growth factors and morphogens, thereby regulating their accessibility and biological activity. Various sulfotransferases and sulfatases with differing spec...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2007-06-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0000575 |
| _version_ | 1830338334400970752 |
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| author | Charles R Holst Hani Bou-Reslan Bryan B Gore Karen Wong Deanna Grant Sreedevi Chalasani Richard A Carano Gretchen D Frantz Marc Tessier-Lavigne Brad Bolon Dorothy M French Avi Ashkenazi |
| author_facet | Charles R Holst Hani Bou-Reslan Bryan B Gore Karen Wong Deanna Grant Sreedevi Chalasani Richard A Carano Gretchen D Frantz Marc Tessier-Lavigne Brad Bolon Dorothy M French Avi Ashkenazi |
| author_sort | Charles R Holst |
| collection | DOAJ |
| description | <h4>Background</h4>Heparan sulfate proteoglycans (HSPGs) use highly sulfated polysaccharide side-chains to interact with several key growth factors and morphogens, thereby regulating their accessibility and biological activity. Various sulfotransferases and sulfatases with differing specificities control the pattern of HSPG sulfation, which is functionally critical. Among these enzymes in the mouse are two secreted 6-O-endosulfatases, Sulf1 and Sulf2, which modify HSPGs in the extracellular matrix and on the cell surface. The roles of Sulf1 and Sulf2 during normal development are not well understood.<h4>Methods/results</h4>To investigate the importance of Sulf1 and Sulf2 for embryonic development, we generated mice genetically deficient in these genes and assessed the phenotypes of the resulting secreted sulfatase-deficient mice. Surprisingly, despite the established crucial role of HSPG interactions during development, neither Sulf1- nor Sulf2-deficient mice showed significant developmental flaws. In contrast, mice deficient in both Sulf1and Sulf2 exhibited highly penetrant neonatal lethality. Loss of viability was associated with multiple, although subtle, developmental defects, including skeletal and renal abnormalities.<h4>Conclusions</h4>These results show that Sulf1 and Sulf2 play overlapping yet critical roles in mouse development and are redundant and essential for neonatal survival. |
| first_indexed | 2024-12-19T20:39:29Z |
| format | Article |
| id | doaj.art-f31aaa63d50d41ba8decee178e62e851 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T20:39:29Z |
| publishDate | 2007-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-f31aaa63d50d41ba8decee178e62e8512022-12-21T20:06:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032007-06-0126e57510.1371/journal.pone.0000575Secreted sulfatases Sulf1 and Sulf2 have overlapping yet essential roles in mouse neonatal survival.Charles R HolstHani Bou-ReslanBryan B GoreKaren WongDeanna GrantSreedevi ChalasaniRichard A CaranoGretchen D FrantzMarc Tessier-LavigneBrad BolonDorothy M FrenchAvi Ashkenazi<h4>Background</h4>Heparan sulfate proteoglycans (HSPGs) use highly sulfated polysaccharide side-chains to interact with several key growth factors and morphogens, thereby regulating their accessibility and biological activity. Various sulfotransferases and sulfatases with differing specificities control the pattern of HSPG sulfation, which is functionally critical. Among these enzymes in the mouse are two secreted 6-O-endosulfatases, Sulf1 and Sulf2, which modify HSPGs in the extracellular matrix and on the cell surface. The roles of Sulf1 and Sulf2 during normal development are not well understood.<h4>Methods/results</h4>To investigate the importance of Sulf1 and Sulf2 for embryonic development, we generated mice genetically deficient in these genes and assessed the phenotypes of the resulting secreted sulfatase-deficient mice. Surprisingly, despite the established crucial role of HSPG interactions during development, neither Sulf1- nor Sulf2-deficient mice showed significant developmental flaws. In contrast, mice deficient in both Sulf1and Sulf2 exhibited highly penetrant neonatal lethality. Loss of viability was associated with multiple, although subtle, developmental defects, including skeletal and renal abnormalities.<h4>Conclusions</h4>These results show that Sulf1 and Sulf2 play overlapping yet critical roles in mouse development and are redundant and essential for neonatal survival.https://doi.org/10.1371/journal.pone.0000575 |
| spellingShingle | Charles R Holst Hani Bou-Reslan Bryan B Gore Karen Wong Deanna Grant Sreedevi Chalasani Richard A Carano Gretchen D Frantz Marc Tessier-Lavigne Brad Bolon Dorothy M French Avi Ashkenazi Secreted sulfatases Sulf1 and Sulf2 have overlapping yet essential roles in mouse neonatal survival. PLoS ONE |
| title | Secreted sulfatases Sulf1 and Sulf2 have overlapping yet essential roles in mouse neonatal survival. |
| title_full | Secreted sulfatases Sulf1 and Sulf2 have overlapping yet essential roles in mouse neonatal survival. |
| title_fullStr | Secreted sulfatases Sulf1 and Sulf2 have overlapping yet essential roles in mouse neonatal survival. |
| title_full_unstemmed | Secreted sulfatases Sulf1 and Sulf2 have overlapping yet essential roles in mouse neonatal survival. |
| title_short | Secreted sulfatases Sulf1 and Sulf2 have overlapping yet essential roles in mouse neonatal survival. |
| title_sort | secreted sulfatases sulf1 and sulf2 have overlapping yet essential roles in mouse neonatal survival |
| url | https://doi.org/10.1371/journal.pone.0000575 |
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