Use of knockout mice to study surfactant protein structure and function.
Pulmonary surfactant protein B (SP-B) is a 79 amino acid peptide that is intimately associated with surfactant phospholipids in the alveolar airspace. Mutations of the SP-B gene that result in complete absence of SP-B are invariably fatal in the neonatal period. The pathology associated with SP-B deficiency suggests that SP-B plays a critical role in integrating the synthesis, assembly and metabolism of the surfactant complex. A strategy is described to elucidate the role of SP-B in surfactant homeostasis by characterizing the pathophysiology associated with cell specific expression of SP-B constructs in vivo. Human SP-B constructs, under control of lung cell-specific promoters, were expressed in SP-B knockout mice in order to achieve expression of the human transgene in a null background. The effect of transgene expression on lung structure and function was assessed by biochemical, morphological and physiological analyses of the surfactant system in fetal and postnatal offspring.
Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA. tim.weaver@chmcc.org
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Weaver
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Beck
D000818:Animals; D019281:Dimerization; D006801:Humans; D008168:Lung / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016296:Mutagenesis; D011510:Proteolipids / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D011663:Pulmonary Surfactants / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*
D011510:Proteolipids; D011663:Pulmonary Surfactants