Surfactant protein B (SP-B) -/- mice are rescued by restoration of SP-B expression in alveolar type II cells but not Clara cells

Surfactant protein B (SP-B) mRNA and protein are restricted to alveolar Typ e II and Clara cells in the respiratory epithelium. In order to investigate the function of SP-B in these distinct cell types, transgenic mice were ge nerated in which SP-B expression was selectively restored in Type II cells or Clara cells of SP-B -/- mice. The 4.8-kilobase murine SP-C promoter was used to generate 3 transgenic lines which expressed human SP-B in Type II c ells (mSP-C/hSP-B). Likewise, the 2.3-kilobase murine CCSP promoter was use d to generate two transgenic lines which expressed human SP-B in Clara cell s (mCCSP/hSP-B). mSP-C/hSP-B and mCCSP/hSP-B transgenic mice were subsequen tly bred to SP-B +/- mice in order to selectively express SP-B in Type II c ells or Clara cells of SP-B -/- mice. Selective restoration of SP-B express ion in Type II cells completely rescued the neonatal lethal phenotype in SP -B -/- mice. Expression of SP-B in some, but not all Type II cells of SP-B -/- mice, allowed postnatal survival, but resulted in significantly altered lung architecture and function. Selective restoration of SP-B expression i n Clara cells of SP-B -/- mice resulted in respiratory dysfunction and inva riable neonatal death, related to the complete absence of mature SP-B pepti de in these mice. These results indicate that expression and processing of the SP-B proprotein to the mature peptide in Type II cells is absolutely re quired for lung function in vivo and that SP-B expression in Clara cells ca nnot substitute for this function.