Targeted inactivation of the murine Abca3 gene leads to respiratory failure in newborns with defective lamellar bodies

Markus Hammel, Geert Michel, Christina Hoefer, Matthias Klaften, Josef Müller-Höcker, Martin Hrabé de Angelis, Andreas Holzinger

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)947-951
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume359
Issue number4
DOIs
StatePublished - 10 Aug 2007
Externally publishedYes

Keywords

  • ABCA3
  • Atelectasis
  • Lamellar body
  • Newborn
  • Respiratory distress syndrome
  • Surfactant
  • Transgenic mouse model

Fingerprint

Dive into the research topics of 'Targeted inactivation of the murine Abca3 gene leads to respiratory failure in newborns with defective lamellar bodies'. Together they form a unique fingerprint.

Cite this