An enhancer region determines hSP-B gene expression in bronchiolar and ATII epithelial cells in transgenic mice.
Regulation of the surfactant protein B gene (SP-B) is developmentally controlled and highly tissue specific. To elucidate the SP-B gene temporal/spatial expression pattern in lung development at the transcriptional level, a transgenic mouse model line carrying the human SP-B (hSP-B) 1.5-kb 5'-flanking regulatory region and the lacZ gene was established. Expression of hSP-B 1.5-kb lacZ gene started at the onset of lung formation [embryonic day 9 (E9)] and was restricted to epithelial cells throughout prenatal and postnatal lung development. In the adult lung, hSP-B 1.5-kb lacZ gene expression was restricted to bronchiolar and alveolar type II epithelial cells. In lung explant culturing studies, the hSP-B 1.5-kb lacZ gene was highly expressed in newly formed epithelial tubules during the respiratory branching process. In a second transgenic mouse line, an enhancer region, which binds to thyroid transcription factor-1, retinoic acid receptor, signal transducers and activators of transcription 3, and nuclear receptor coactivators (SRC-1, ACTR, TIF2, and CBP/p300), was deleted from the hSP-B 1.5-kb lacZ gene. The deletion abolished hSP-B lacZ gene expression in bronchiolar epithelial cells and significantly reduced its expression level in alveolar type II epithelial cells in transgenic mice.
Yang
Li
L
Division of Pulmonary Biology, Graduate Program for Molecular and Developmental Biology, and Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
Naltner
Angela
A
Kreiner
Allison
A
Yan
Dong
D
Cowen
Angelynn
A
Du
Hong
H
Yan
Cong
C
D000818:Animals; D001980:Bronchi / Q000166:cytology; D004742:Enhancer Elements, Genetic; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D016297:Mutagenesis, Site-Directed; D009928:Organ Specificity; D011650:Pulmonary Alveoli / Q000166:cytology; D037701:Pulmonary Surfactant-Associated Protein B / Q000235:genetics* / Q000378:metabolism; D017384:Sequence Deletion
D037701:Pulmonary Surfactant-Associated Protein B