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 in timately associated with surfactant phospholipids in the alveolar airspace, Mutations of the SP-B gene that result in complete absence of SP-B are inv ariably fatal in the neonatal period. The pathology associated with SP-B de ficiency suggests that SP-B plays a critical role in integrating the synthe sis, assembly a nd metabolism of the surfactant complex. A strategy is desc ribed to elucidate the role of SP-B in surfactant homeostasis by characteri zing the pathophysiology associated with cell specific expression of SP-B c onstructs in vivo. Human SP-B constructs, under control of lung cell-specif ic promoters, were expressed in SP-B knockout mice in order to achieve expr ession of the human transgene in a null background. The effect of transgene expression on lung structure and function was assessed by biochemical, mor phological and physiological analyses of the surfactant system in fetal and postnatal offspring.