Aquaporin-5 expression, but not other peripheral lung marker genes, is reduced in PTH/PTHrP receptor null mutant fetal mice

Parathyroid hormone-related peptide (PTHrP) and the parathyroid hormone/par athyroid hormone-related peptide (PTH/PTHrP) receptor are important develop mental regulators of cell growth and differentiation in some organs. In lun g, both the peptide and the receptor are expressed early in development and in alveolar cells in adults. In adult alveolar cells, PTHrP appears to pro mote the alveolar type II cell phenotype in vitro. Mice carrying null mutat ions in genes for either receptor or ligand die at birth of respiratory fai lure. To determine if absence of the PTH/PTHrP receptor alters morphogenesi s or cellular differentiation of the distal lung, we analyzed the morpholog y and gene expression patterns in PTH/PTHrP receptor null mutant mice right before birth and compared them with wild-type and heterozygous null litter mates. Using semiquantitative Northern blots, we observed that messenger RN A (mRNA) for aquaporin-5, the type I cell-specific water channel, was marke dly decreased. The abundance of other marker mRNAs for type I and type II c ell phenotypes, including T1 alpha, surfactant proteins, and others, was un altered. Gross morphology and lung pattern, assessed by in situ hybridizati on for surfactant protein C, were normal. We conclude therefore that, altho ugh signaling through this receptor may influence expression of specific lu ng genes, it does not play a major role in the general regulation of lung d evelopment and growth.