Human surfactant protein B promoter in transgenic mice: temporal, spatial, and stimulus-responsive regulation

Strayer, Marlene S.; Savani, Rashmin C.; Gonzales, Linda W.; Zaman, Asad; Cui, Zheng; Veszelovszky, Edina; Wood, Emily J.; Ho, Ye Shih; Ballard, Philip L.

doi:10.1152/ajplung.00188.2001

Cited by 15 publications

(10 citation statements)

References 56 publications

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“…Three recent reports have assessed SP-B promoter activity in transgenic mice. A Ϫ1,039-to ϩ431-bp segment of the human SP-B promoter generated bronchoalveolar expression and low-level thyroid, trachea, and intestine expression (21). A separate study of the human SP-B promoter demonstrated that 1.5 kb directs lung and intestine expression in mice.…”

Section: Discussionmentioning

confidence: 99%

The murine SP-C promoter directs type II cell-specific expression in transgenic mice

Glasser

Eszterhas

Detmer

et al. 2005

American Journal of Physiology-Lung Cellular and Molecular Phys

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Section: Discussionmentioning

confidence: 99%

The murine SP-C promoter directs type II cell-specific expression in transgenic mice

Glasser

Eszterhas

Detmer

et al. 2005

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…AC109608). Furthermore, previous studies have established that a variety of human gene promoters are active in vivo using transgenic mice (2,24,37). Interestingly, the pattern of expression of the hSMVT promoter-luciferase transgene was found to be similar to that of the mouse endogenous SMVT message, especially in the different regions of the intestinal tract.…”

Section: Discussionmentioning

confidence: 84%

Regulation of the human biotin transporter hSMVT promoter by KLF-4 and AP-2: confirmation of promoter activity in vivo

Reidling¹,

Said²

2007

American Journal of Physiology-Cell Physiology

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The mechanism of biotin uptake in human intestine has been well characterized and involves the human sodium-dependent multivitamin transporter (hSMVT), yet little is known about the molecular/transcriptional regulation of the system. Previous investigations cloned the 5' regulatory region of the hSMVT gene and identified the minimal promoter. To expand these investigations, we compared activity of the hSMVT promoter in three human intestinal epithelial cell lines (NCM460, Caco-2, and HuTu-80) and contrasted a renal epithelial cell line (HEK-293). We analyzed the role of putative cis-elements in regulating promoter activity and confirmed activity of the cloned hSMVT promoter in vivo. In vitro studies demonstrated that all cell lines utilized the same minimal promoter region, and mutation of specific cis-regulatory elements [Kruppel-like factor 4 (KLF-4) and activator protein-2 (AP-2)] led to a decrease in promoter activity in all intestinal cell types but not in renal cells. Using electrophoretic mobility shift assays, we identified two specific DNA/protein complexes. Using oligonucleotide competition and antibody supershift analysis, we determined that KLF-4 and AP-2 were involved in forming the complexes. In HEK-293 cells, overexpressing KLF-4 increased the endogenous hSMVT message levels threefold and activated a cotransfected hSMVT promoter-reporter construct. In vivo studies using hSMVT promoter-luciferase transgenic mice established physiological relevance and showed the pattern of hSMVT promoter expression to be similar to endogenous mouse SMVT mRNA expression. The results demonstrate, for the first time, the importance of KLF-4 and AP-2 in regulating the activity of the hSMVT promoter in the intestine and provide direct in vivo confirmation of hSMVT promoter activity.

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“…4A). 34,42, and 66 transgenic lines, confirming that the 4.3-kb Aqp5 promoter is only sufficient to drive high-level salivary gland-specific gene expression. 14, 34, 42, and 66) were identified.…”

Section: Identification Of Aqp5-egfp Transgenic Mice the Aqp5mentioning

confidence: 80%

Rat aquaporin-5 4.3-kb 5′-flanking region differentially regulates expression in salivary gland and lung in vivo

Zhou¹,

Ann²,

Flodby³

et al. 2008

American Journal of Physiology-Cell Physiology

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We previously cloned a 4.3-kb genomic fragment encompassing 5'-flanking regulatory elements of rat aquaporin-5 (Aqp5) that demonstrated preferential transcriptional activity in lung and salivary cells in vitro. To investigate the ability of Aqp5 regulatory elements to direct transgene expression in vivo, transgenic (TG) mice and rats were generated in which the 4.3-kb Aqp5 fragment directed the expression of enhanced green fluorescent protein (EGFP). RT-PCR revealed relative promoter specificity for the lung and salivary glands in TG mice. Immunofluorescence microscopy showed strong EGFP expression in salivary acinar cells but not in lung type I (AT1) cells, both known sites of endogenous AQP5 expression. Similar results were obtained in TG rats generated by lentiviral transgenesis. EGFP mRNA was detected in both salivary glands and lung. Robust EGFP fluorescence was observed in frozen sections of the rat salivary gland but not in the lung or other tested tissues. The percentage of EGFP-positive acinar cells was increased in parotid and submandibular glands of TG rats receiving a chronic injection of the beta-adrenergic receptor agonist isoproterenol. EGFP-positive cells in the lung that were also reactive with the AT1-cell specific monoclonal antibody VIIIB2 were identified by flow cytometry. These findings demonstrate that the 4.3-kb Aqp5 promoter/enhancer directs strong cell-specific transgene expression in salivary gland and low-level AT1 cell-specific expression in the lung. While these Aqp5 regulatory elements should be useful for functional studies in salivary glands, additional upstream or intronic cis-active elements are likely required for robust expression in the lung.

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Human surfactant protein B promoter in transgenic mice: temporal, spatial, and stimulus-responsive regulation

Cited by 15 publications

References 56 publications

The murine SP-C promoter directs type II cell-specific expression in transgenic mice

The murine SP-C promoter directs type II cell-specific expression in transgenic mice

Regulation of the human biotin transporter hSMVT promoter by KLF-4 and AP-2: confirmation of promoter activity in vivo

Rat aquaporin-5 4.3-kb 5′-flanking region differentially regulates expression in salivary gland and lung in vivo

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