| First Author | Herber-Jonat S | Year | 2013 |
| Journal | Pediatr Res | Volume | 74 |
| Issue | 4 | Pages | 384-92 |
| PubMed ID | 23881110 | Mgi Jnum | J:234008 |
| Mgi Id | MGI:5788723 | Doi | 10.1038/pr.2013.127 |
| Citation | Herber-Jonat S, et al. (2013) Abca3 haploinsufficiency is a risk factor for lung injury induced by hyperoxia or mechanical ventilation in a murine model. Pediatr Res 74(4):384-92 |
| abstractText | 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. |
