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

Pediatr Res. 2013 Oct;74(4):384-92. doi: 10.1038/pr.2013.127. Epub 2013 Jul 23.


Background: Heterozygous ATP-binding-cassette subfamily A member 3 (ABCA3) mutations are associated with neonatal respiratory complications. In an adult murine model, we investigated 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 h of hyperoxia or left unchallenged in air.

Results: As compared with WT mice, 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / genetics*
  • Analysis of Variance
  • Animals
  • Blotting, Western
  • Bronchoalveolar Lavage Fluid / chemistry
  • DNA Primers / genetics
  • Genetic Predisposition to Disease / genetics*
  • Haploinsufficiency / genetics*
  • Histological Techniques
  • Hyperoxia / complications*
  • Interleukins / analysis
  • Lung / metabolism
  • Lung / pathology
  • Lung Compliance / physiology
  • Mice
  • Phosphatidylcholines / analysis
  • Phosphatidylglycerols / analysis
  • Real-Time Polymerase Chain Reaction
  • Respiration, Artificial / adverse effects*
  • Respiratory Distress Syndrome / etiology*
  • Respiratory Distress Syndrome / genetics


  • ATP-Binding Cassette Transporters
  • Abca3 protein, mouse
  • DNA Primers
  • Interleukins
  • Phosphatidylcholines
  • Phosphatidylglycerols