ABCA3 is critical for lamellar body biogenesis in vivo

Naeun Cheong, Huayan Zhang, Muniswamy Madesh, Ming Zhao, Kevin Yu, Chandra Dodia, Aron B. Fisher, Rashmin C. Savani, Henry Shuman

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

Mutations in ATP-binding cassette transporter A3 (human ABCA3) protein are associated with fatal respiratory distress syndrome in newborns. We therefore characterized mice with targeted disruption of the ABCA3 gene. Homozygous Abca3-/- knock-out mice died soon after birth, whereas most of the wild type, Abca3+/+, and heterozygous, Abca3+/-, neonates survived. The lungs from E18.5 and E19.5 Abca3-/- mice were less mature than wild type. Alveolar type 2 cells from Abca3-/- embryos contained no lamellar bodies, and expression of mature SP-B protein was disrupted when compared with the normal lung surfactant system of wild type embryos. Small structural and functional differences in the surfactant system were seen in adult Abca3+/- compared with Abca3+/+ mice. The heterozygotes had fewer lamellar bodies, and the incorporation of radiolabeled substrates into newly synthesized disaturated phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine, and phosphatidylserine in both lamellar bodies and surfactant was lower than in Abca3+/+ mouse lungs. In addition, since the fraction of near term Abca3-/- embryos was significantly lower than expected from Mendelian inheritance ABCA3 probably plays roles in development unrelated to surfactant. Collectively, these findings strongly suggest that ABCA3 is necessary for lamellar body biogenesis, surfactant protein-B processing, and lung development late in gestation.

Original languageEnglish (US)
Pages (from-to)23811-23817
Number of pages7
JournalJournal of Biological Chemistry
Volume282
Issue number33
DOIs
StatePublished - Aug 17 2007

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Surface-Active Agents
Lung
Embryonic Structures
Pulmonary Surfactant-Associated Protein B
Newborn Respiratory Distress Syndrome
Alveolar Epithelial Cells
Phosphatidylglycerols
ATP-Binding Cassette Transporters
Phosphatidylserines
Heterozygote
Knockout Mice
Genes
Parturition
Pregnancy
Mutation
Substrates
Processing

ASJC Scopus subject areas

  • Biochemistry

Cite this

Cheong, N., Zhang, H., Madesh, M., Zhao, M., Yu, K., Dodia, C., ... Shuman, H. (2007). ABCA3 is critical for lamellar body biogenesis in vivo. Journal of Biological Chemistry, 282(33), 23811-23817. https://doi.org/10.1074/jbc.M703927200

ABCA3 is critical for lamellar body biogenesis in vivo. / Cheong, Naeun; Zhang, Huayan; Madesh, Muniswamy; Zhao, Ming; Yu, Kevin; Dodia, Chandra; Fisher, Aron B.; Savani, Rashmin C.; Shuman, Henry.

In: Journal of Biological Chemistry, Vol. 282, No. 33, 17.08.2007, p. 23811-23817.

Research output: Contribution to journalArticle

Cheong, N, Zhang, H, Madesh, M, Zhao, M, Yu, K, Dodia, C, Fisher, AB, Savani, RC & Shuman, H 2007, 'ABCA3 is critical for lamellar body biogenesis in vivo', Journal of Biological Chemistry, vol. 282, no. 33, pp. 23811-23817. https://doi.org/10.1074/jbc.M703927200
Cheong N, Zhang H, Madesh M, Zhao M, Yu K, Dodia C et al. ABCA3 is critical for lamellar body biogenesis in vivo. Journal of Biological Chemistry. 2007 Aug 17;282(33):23811-23817. https://doi.org/10.1074/jbc.M703927200
Cheong, Naeun ; Zhang, Huayan ; Madesh, Muniswamy ; Zhao, Ming ; Yu, Kevin ; Dodia, Chandra ; Fisher, Aron B. ; Savani, Rashmin C. ; Shuman, Henry. / ABCA3 is critical for lamellar body biogenesis in vivo. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 33. pp. 23811-23817.
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