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.
MeSH terms
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Amidohydrolases / genetics*
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Animals
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Animals, Newborn
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Cell Differentiation
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Epithelial Cells / pathology
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Gene Deletion*
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Humans
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Infant, Newborn
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Lung / chemistry
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Lung / embryology
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Lung / pathology*
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Lung / physiopathology*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Microscopy, Electron
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Phosphatidylcholines / analysis
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Phospholipids / analysis
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Pulmonary Atelectasis / genetics
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Pulmonary Atelectasis / mortality
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Pulmonary Atelectasis / pathology
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Pulmonary Atelectasis / physiopathology
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Pulmonary Surfactants / analysis
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Respiratory Distress Syndrome, Newborn / enzymology*
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Respiratory Distress Syndrome, Newborn / genetics
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Respiratory Distress Syndrome, Newborn / pathology*
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Respiratory Distress Syndrome, Newborn / physiopathology
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Sulfotransferases / genetics*
Substances
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Phosphatidylcholines
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Phospholipids
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Pulmonary Surfactants
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lecithins, disaturated
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Sulfotransferases
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heparitin sulfotransferase
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Amidohydrolases