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/parathyroid hormone-related peptide (PTH/PTHrP) receptor are important developmental regulators of cell growth and differentiation in some organs. In lung, both the peptide and the receptor are expressed early in development and in alveolar cells in adults. In adult alveolar cells, PTHrP appears to promote the alveolar type II cell phenotype in vitro. Mice carrying null mutations in genes for either receptor or ligand die at birth of respiratory failure. To determine if absence of the PTH/PTHrP receptor alters morphogenesis or cellular differentiation of the distal lung, we analyzed the morphology and gene expression patterns in PTH/PTHrP receptor null mutant mice right before birth and compared them with wild-type and heterozygous null littermates. Using semiquantitative Northern blots, we observed that messenger RNA (mRNA) for aquaporin-5, the type I cell-specific water channel, was markedly decreased. The abundance of other marker mRNAs for type I and type II cell phenotypes, including T1alpha, surfactant proteins, and others, was unaltered. Gross morphology and lung pattern, assessed by in situ hybridization for surfactant protein C, were normal. We conclude therefore that, although signaling through this receptor may influence expression of specific lung genes, it does not play a major role in the general regulation of lung development and growth.
Ramirez
M I
MI
The Pulmonary Center, Department of Medicine and Anatomy, Boston University School of Medicine, Massachusetts 02118, USA. mramirez@bupula.bu.edu
Chung
U I
UI
Williams
M C
MC
D000818:Animals; D051402:Aquaporin 5; D020346:Aquaporins / Q000235:genetics*; D015415:Biomarkers; D051242:Caveolin 1; D022461:Caveolins; D002454:Cell Differentiation / Q000502:physiology; D004847:Epithelial Cells / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D005333:Fetus / Q000737:chemistry / Q000166:cytology; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006023:Glycoproteins / Q000235:genetics; D006133:Growth Substances / Q000235:genetics; D017403:In Situ Hybridization; D008168:Lung / Q000166:cytology / Q000196:embryology / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D010281:Parathyroid Hormone / Q000235:genetics*; D011510:Proteolipids / Q000235:genetics; D037663:Pulmonary Surfactant-Associated Protein D; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D018016:Receptors, Parathyroid Hormone / Q000235:genetics*
C496038:Aqp5 protein, mouse; D051402:Aquaporin 5; D020346:Aquaporins; D015415:Biomarkers; D051242:Caveolin 1; D022461:Caveolins; C496454:Fgf7 protein, mouse; D051526:Fibroblast Growth Factor 10; D006023:Glycoproteins; D006133:Growth Substances; D008565:Membrane Proteins; D010281:Parathyroid Hormone; D011510:Proteolipids; D037663:Pulmonary Surfactant-Associated Protein D; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D018016:Receptors, Parathyroid Hormone; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors