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Targeted disruption of the surfactant protein B gene disrupts surfactant homeostasis, causing respiratory failure in newborn mice.
Open accessAbstract
Surfactant protein B (SP-B) is an 8.7-kDa, hydrophobic protein that enhances the spreading and stability of surfactant phospholipids in the alveolus. To further assess the role of SP-B in lung function, the SP-B gene was disrupted by homologous recombination in murine mouse embryonic stem cells. Mice with a single mutated SP-B allele (+/-) were unaffected, whereas homozygous SP-B -/- offspring died of respiratory failure immediately after birth. Lungs of SP-B -/- mice developed normally but remained atelectatic in spite of postnatal respiratory efforts. SP-B protein and mRNA were undetectable and tubular myelin figures were lacking in SP-B -/- mice. Type II cells of SP-B -/- mice contained no fully formed lamellar bodies. While the abundance of SP-A and SP-C mRNAs was not altered, an aberrant form of pro-SP-C, 8.5 kDa, was detected, and fully processed SP-C peptide was markedly decreased in lung homogenates of SP-B -/- mice. Ablation of the SP-B gene disrupts the routing, storage, and function of surfactant phospholipids and proteins, causing respiratory failure at birth.
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Cited by
Sanford, L. P., Ormsby, I., Groot, A. C. G.-D., Sariola, H., Friedman, R., Boivin, G. P., Cardell, E. L., & Doetschman, T. (1997) · Development · doi:10.1242/dev.124.13.2659 · Cited by 1,447
A Mutation in the Surfactant Protein C Gene Associated with Familial Interstitial Lung Disease
Nogee, L. M., Dunbar, A. E., Wert, S. E., Askin, F., Hamvas, A., & Whitsett, J. A. (2001) · New England Journal of Medicine · doi:10.1056/nejm200102223440805 · Cited by 929
Self-citationWillson, D. F. (2005) · JAMA · doi:10.1001/jama.293.4.470 · Cited by 420
Choreoathetosis, hypothyroidism, and pulmonary alterations due to human NKX2-1 haploinsufficiency
Krude, H., Schütz, B., Biebermann, H., von Moers, A., Schnabel, D., Neitzel, H., Tönnies, H., Weise, D., Lafferty, A., Schwarz, S., et al. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0214341 · Cited by 268
Shen, Y., Schlessinger, K., Zhu, X., Meffre, E., Quimby, F., Levy, D. E., & Darnell, J. E. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.1.407-419.2004 · Cited by 200
Metadata
- Authors
- Clark, J. C., Wert, S. E., Bachurski, C. J., Stahlman, M. T., Stripp, B. R., Weaver, T. E., & Whitsett, J. A.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1995-08-15
- Volume
- 92
- Issue
- 17
- Pages
- 7794-7798
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1990402565
- Cited by
- 642
- References
- 0
- FWCI
- 24.60
- Type
- journal article
- Language
- en
- Open access
- green
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- Clark, J. C., Wert, S. E., Bachurski, C. J., Stahlman, M. T., Stripp, B. R., Weaver, T. E., & Whitsett, J. A. (1995). Targeted disruption of the surfactant protein B gene disrupts surfactant homeostasis, causing respiratory failure in newborn mice. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.92.17.7794
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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