1.3 kilobases of the lung type I cell T1alpha gene promoter mimics endogenous gene expression patterns during development but lacks sequences to enhance expression in perinatal and adult lung.
The T1alpha gene is one of few markers for the type I cell phenotype in the adult mammalian lung. Type I cells form a large, thin epithelial layer that facilitates gas exchange and transport of fluids between the air spaces and capillaries. The T1alpha gene has a complex pattern of developmental expression in lung and brain; in vitro studies indicate that expression is regulated in part by thyroid transcription factor 1, forkhead proteins, and Sp1/Sp3 proteins. To explore the mechanisms that confine T1alpha expression in intact adult animals to alveolar type I and choroid plexus epithelial cells, we generated mice bearing a 1.3-kb T1alpha promoter-chloramphenicol acetyltransferase (CAT) gene. In situ hybridization and RNase protection assays show that the 1.3-kb promoter confers a pattern of CAT expression that largely matches the endogenous T1alpha in embryos and mid-term fetuses in lung and central nervous system. However, the 1.3-kb promoter lacks elements important for perinatal up-regulation of T1alpha in the lung and maintenance of that expression in the adult lung and brain. The final adult pattern of T1alpha expression may be directed by elements outside the 1.3-kb fragment, perhaps those 5' to the 1.3-kb fragment as we show herein, or in 3' and intronic regions. Dev Dyn 1999;215:319-331.
The Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA. mramirez@bupula.bu.edu
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Ramirez
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Williams
D000818:Animals; D001842:Bone and Bones / Q000033:anatomy & histology / Q000196:embryology; D001921:Brain / Q000033:anatomy & histology / Q000196:embryology; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D004064:Digestive System / Q000033:anatomy & histology / Q000196:embryology; D004847:Epithelial Cells / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018859:Hair Follicle / Q000033:anatomy & histology / Q000196:embryology; D006321:Heart / Q000033:anatomy & histology / Q000196:embryology; D017403:In Situ Hybridization; D007668:Kidney / Q000033:anatomy & histology / Q000196:embryology; D008168:Lung / Q000196:embryology* / Q000502:physiology; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D011401:Promoter Regions, Genetic; D012469:Salivary Glands / Q000033:anatomy & histology / Q000196:embryology; D013116:Spinal Cord / Q000033:anatomy & histology / Q000196:embryology; D013997:Time Factors; D014018:Tissue Distribution; D000098853:Podoplanin
D015500:Chloramphenicol O-Acetyltransferase; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C490441:Pdpn protein, mouse; D000098853:Podoplanin