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Open Access Green as soon as Postprint is submitted to ZB.
Targeted inactivation of the murine Abca3 gene leads to respiratory failure in newborns with defective lamellar bodies.
Biochem. Biophys. Res. Commun. 359, 947-951 (2007)
Mutations in the human ABCA3 gene, encoding an ABC-transporter, are associated with respiratory failure in newborns and pediatric interstitial lung disease. In order to study disease mechanisms, a transgenic mouse model with a disrupted Abca3 gene was generated by targeting embryonic stem cells. While heterozygous animals developed normally and were fertile, individuals homozygous for the altered allele (Abca3-/-) died within one hour after birth from respiratory failure, ABCA3 protein being undetectable. Abca3-/- newborns showed atelectasis of the lung in comparison to a normal gas content in unaffected or heterozygous littermates. Electron microscopy demonstrated the absence of normal lamellar bodies in type II pneumocytes. Instead, condensed structures with apparent absence of lipid content were found. We conclude that ABCA3 is required for the formation of lamellar bodies and lung surfactant function. The phenotype of respiratory failure immediately after birth corresponds to the clinical course of severe ABCA3 mutations in human newborns.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
ABCA3; Transgenic mouse model; Lamellar body; Respiratory distress syndrome; Surfactant; Newborn; Atelectasis
ISSN (print) / ISBN
0006-291X
e-ISSN
1090-2104
Quellenangaben
Volume: 359,
Issue: 4,
Pages: 947-951
Publisher
Elsevier
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Experimental Genetics (IEG)