An alternatively spliced surfactant protein B mRNA in normal human lung: disease implication

We identified an alternatively-spliced surfactant protein B (SP-B) mRNA fro m normal human lung with a 12 nt deletion at the beginning of exon 8. This deletion causes a loss of four amino acids in the SP-B precursor protein. S equence comparison of the 3' splice sites reveals only one difference in th e frequency of U/C in the 11 predominantly-pyrimidine nucleotide tract, 73% for the normal and 45% for the alternatively-spliced SP-B mRNA (77-99% for the consensus sequence). Analysis of SP-B mRNA in lung indicates that the abundance of the alternatively-spliced form is very low and varies among in dividuals. Although the relative abundance of the deletion form of SP-B mRN A remains constant among normal lungs, it is found with relatively higher a bundance in the lungs of some individuals with diseases such as congenital alveolar proteinosis, respiratory distress syndrome, bronchopulmonary dyspl asia, alveolar capillary dysplasia and hypophosphatasia. This observation p oints to the possibility that the alternative splicing is a potential regul atory mechanism of SP-B and may play a role in the pathogenesis of disease under certain circumstances.