title: Targeted disruption of NDST-1 gene leads to pulmonary hypoplasia and neonatal respiratory distress in mice.
abstract: In order to address the biological function of GlcNAc N-deacetylase/N-sulfotransferase-1 (NDST-1), we disrupted the NDST-1 gene by homologous recombination in mouse embryonic stem cells. The NDST-1 null mice developed respiratory distress and atelectasis that subsequently caused neonatal death. Morphological examination revealed type II pneumocyte immaturity, which was characterized by an increased glycogen content and a reduced number of lamellar bodies and microvilli. Biochemical analysis further indicated that both total phospholipids and disaturated phosphatidylcholine were reduced in the mutant lung. Our data revealed that NDST-1 was essential for the maturation of type II pneumocytes and its inactivation led to a neonatal respiratory distress syndrome.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
authors.forename: G
authors.initials: G
authors.lastname: Fan
authors.forename: L
authors.initials: L
authors.lastname: Xiao
authors.forename: L
authors.initials: L
authors.lastname: Cheng
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: B
authors.initials: B
authors.lastname: Sun
authors.forename: G
authors.initials: G
authors.lastname: Hu
mesh_terms: D000581:Amidohydrolases / Q000235:genetics*; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation; D004847:Epithelial Cells / Q000473:pathology; D017353:Gene Deletion; D006801:Humans; D007231:Infant, Newborn; D008168:Lung / Q000737:chemistry / Q000196:embryology / Q000473:pathology* / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D010713:Phosphatidylcholines / Q000032:analysis; D010743:Phospholipids / Q000032:analysis; D001261:Pulmonary Atelectasis / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D011663:Pulmonary Surfactants / Q000032:analysis; D012127:Respiratory Distress Syndrome, Newborn / Q000201:enzymology* / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D015238:Sulfotransferases / Q000235:genetics*
chemical_list: D010713:Phosphatidylcholines; D010743:Phospholipids; D011663:Pulmonary Surfactants; C017463:lecithins, disaturated; D015238:Sulfotransferases; C021350:heparitin sulfotransferase; D000581:Amidohydrolases