title: Secreted sulfatases Sulf1 and Sulf2 have overlapping yet essential roles in mouse neonatal survival.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  These results show that Sulf1 and Sulf2 play overlapping yet critical roles in mouse development and are redundant and essential for neonatal survival.
authors.affiliation: Department of Molecular Oncology, Genentech, Inc., South San Francisco, California, United States of America.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Holst
authors.forename: Hani
authors.initials: H
authors.lastname: Bou-Reslan
authors.forename: Bryan B
authors.initials: BB
authors.lastname: Gore
authors.forename: Karen
authors.initials: K
authors.lastname: Wong
authors.forename: Deanna
authors.initials: D
authors.lastname: Grant
authors.forename: Sreedevi
authors.initials: S
authors.lastname: Chalasani
authors.forename: Richard A
authors.initials: RA
authors.lastname: Carano
authors.forename: Gretchen D
authors.initials: GD
authors.lastname: Frantz
authors.forename: Marc
authors.initials: M
authors.lastname: Tessier-Lavigne
authors.forename: Brad
authors.initials: B
authors.lastname: Bolon
authors.forename: Dorothy M
authors.initials: DM
authors.lastname: French
authors.forename: Avi
authors.initials: A
authors.lastname: Ashkenazi
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development*; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D047108:Embryonic Development; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005804:Genes, Lethal / Q000502:physiology*; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D017403:In Situ Hybridization; D007668:Kidney / Q000002:abnormalities; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000002:abnormalities; D011247:Pregnancy; D015398:Signal Transduction; D013429:Sulfatases / Q000502:physiology*; D015238:Sulfotransferases / Q000502:physiology*; D015996:Survival Rate
chemical_list: D019812:Heparan Sulfate Proteoglycans; C486773:Sulf1 protein, mouse; D015238:Sulfotransferases; C514911:Sulf2 protein, mouse; D013429:Sulfatases