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.
Weaver
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Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA. tim.weaver@chmcc.org
Beck
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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