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Herber-Jonat, S.* ; Mittal, R.* ; Huppmann, M.* ; Hammel, M.* ; Liebisch, G.* ; Yildirim, A.Ö. ; Eickelberg, O. ; Schmitz, G.* ; Hrabě de Angelis, M. ; Flemmer, A.W.* ; Holzinger, A.*

Abca3 haploinsufficiency is a risk factor for lung injury induced by hyperoxia or mechanical ventilation in a murine model.

Pediatr. Res. 74, 384-392 (2013)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Background:Heterozygous ABCA3 (ATP-binding-cassette sub-family A member3) mutations are associated with neonatal respiratory complications. We investigated in an adult murine model whether Abca3 haploinsufficiency is a predisposing factor for lung injury induced by hyperoxia or mechanical ventilation.Methods:Abca3 haploinsufficient (Abca3+/-) and wild-type (WT) mice were prospectively randomized to 25 min of ventilation or 72 hours of hyperoxia or left unchallenged in air.Results:As compared to WT, unchallenged Abca3+/- mice had significantly decreased lung phosphatidylcholine (PC) and phosphatidylglycerol (PG) levels (p<0.02) and decreased lung compliance (p<0.05). When ventilated for 25 min, Abca3+/- mice demonstrated a significantly greater increase in bronchoalveolar lavage (BAL) interleukins (p<0.01) and lung wet to dry ratio (p<0.005). Hyperoxia resulted in increased compliance (p<0.05) and total lung capacity (TLC) (p=0.01) only in the Abca3+/- mice consistent with enlarged alveolar spaces. The ratio of PC to PG in BAL - relevant for surfactant dysfunction - was significantly elevated by oxygen exposure with the greatest increase in Abca3+/- mice.Conclusions:In a murine model, Abca3 haploinsufficiency results in an altered biochemical and lung mechanical phenotype as well as a greater lung injury induced by hyperoxia or mechanical ventilation. The inability to maintain a normal PC/PG ratio appears to play a key role.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Tandem Mass-spectrometry ; Pulmonary Surfactant ; Respiratory-distress ; Ii Cells ; Mutations ; Deficiency ; Disease ; Protein ; Mice ; Phosphatidylglycerol
ISSN (print) / ISBN 0031-3998
e-ISSN 1530-0447
Journal Pediatric Research
Quellenangaben Volume: 74, Issue: 4, Pages: 384-392 Article Number: , Supplement: ,
Publisher Lippincott Williams & Wilkins
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Lung Health and Immunity (LHI)
Institute of Experimental Genetics (IEG)
Institute of Lung Biology (LHI)