scholarly journals Regulation of expression of a sheep metallothionein 1a-sheep growth hormone fusion gene in transgenic mice.

1989 ◽  
Vol 9 (12) ◽  
pp. 5473-5479 ◽  
Author(s):  
C M Shanahan ◽  
N W Rigby ◽  
J D Murray ◽  
J T Marshall ◽  
C A Townrow ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Transgenic Mice ◽  
Mrna Expression ◽  
Transgene Expression ◽  
Fusion Gene ◽  
Developmental Expression ◽  
Regulation Of Expression ◽  
Tissue Specific ◽  
Transgenic Livestock ◽  
Main Regulator

Transgenic mice containing a sheep metallothionein 1a-sheep growth hormone fusion gene exhibited low, tissue-specific basal levels of transgene mRNA expression, resulting in slightly elevated levels of circulating growth hormone that did not lead to a detectable increase in growth. After zinc stimulation, high levels of transgene mRNA expression were induced in a number of tissues; these levels correlated with increased levels of circulating growth hormone, resulting in growth increases of up to 1.5 times the levels of controls and unstimulated transgenic mice. After removal of the zinc stimulus, transgene expression and circulating growth hormone concentrations returned to basal levels. Additional evidence from the pattern of developmental expression of the transgene suggests that zinc is the main regulator of this promoter in mice. The demonstrated regulation and low basal level of expression of the sheep metallothionein 1a promoter make it a candidate for use in other mouse transgenic studies and for use in transgenic livestock, in which regulation of expression is essential.

Regulation of expression of a sheep metallothionein 1a-sheep growth hormone fusion gene in transgenic mice

1989 ◽  
Vol 9 (12) ◽  
pp. 5473-5479
Author(s):  
C M Shanahan ◽  
N W Rigby ◽  
J D Murray ◽  
J T Marshall ◽  
C A Townrow ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Transgenic Mice ◽  
Mrna Expression ◽  
Transgene Expression ◽  
Fusion Gene ◽  
Developmental Expression ◽  
Regulation Of Expression ◽  
Tissue Specific ◽  
Transgenic Livestock ◽  
Main Regulator

Transgenic mice containing a sheep metallothionein 1a-sheep growth hormone fusion gene exhibited low, tissue-specific basal levels of transgene mRNA expression, resulting in slightly elevated levels of circulating growth hormone that did not lead to a detectable increase in growth. After zinc stimulation, high levels of transgene mRNA expression were induced in a number of tissues; these levels correlated with increased levels of circulating growth hormone, resulting in growth increases of up to 1.5 times the levels of controls and unstimulated transgenic mice. After removal of the zinc stimulus, transgene expression and circulating growth hormone concentrations returned to basal levels. Additional evidence from the pattern of developmental expression of the transgene suggests that zinc is the main regulator of this promoter in mice. The demonstrated regulation and low basal level of expression of the sheep metallothionein 1a promoter make it a candidate for use in other mouse transgenic studies and for use in transgenic livestock, in which regulation of expression is essential.

Analysis of genomic regions involved in regulation of the rabbit surfactant protein A gene in transgenic mice

1999 ◽  
Vol 277 (2) ◽  
pp. L349-L361 ◽  
Author(s):  
Joseph L. Alcorn ◽  
Robert E. Hammer ◽  
Katherine R. Graves ◽  
Margaret E. Smith ◽  
Shanna D. Maika ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transgenic Mice ◽  
Transgene Expression ◽  
Fusion Gene ◽  
Surfactant Protein ◽  
Type Ii Cells ◽  
Type Ii ◽  
Regulation Of Expression ◽  
Camp Induction ◽  
Genomic Regions

The gene encoding surfactant protein (SP) A, a developmentally regulated pulmonary surfactant-associated protein, is expressed in a lung-specific manner, primarily in pulmonary type II cells. SP-A gene transcription in the rabbit fetal lung is increased by cAMP. To delineate the genomic regions involved in regulation of SP-A gene expression, lines of transgenic mice carrying fusion genes composed of various amounts of 5′-flanking DNA from the rabbit SP-A gene linked to the human growth hormone structural gene as a reporter were established. We found that as little as 378 bp of 5′-flanking DNA was sufficient to direct appropriate lung cell-selective and developmental regulation of transgene expression. The same region was also sufficient to mediate cAMP induction of transgene expression. Mutagenesis or deletion of either of two DNA elements, proximal binding element and a cAMP response element-like sequence, previously found to be crucial for cAMP induction of SP-A promoter activity in transfected type II cells, did not affect lung-selective or temporal regulation of expression of the transgene; however, overall levels of fusion gene expression were reduced compared with those of wild-type transgenes.

Tissue-specific and developmental expression of human transthyretin gene in transgenic mice

1987 ◽  
Vol 8 (4) ◽  
pp. 195-205 ◽  
Author(s):  
Ken-Ichi Yamamura ◽  
Shoji Wakasugi ◽  
Shuichiro Maeda ◽  
Takeaki Inomoto ◽  
Tomohisa Iwanaga ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Developmental Expression ◽  
Tissue Specific

scholarly journals Tissue-specific expression of a FMR1/β-galactosidase fusion gene in transgenic mice

1995 ◽  
Vol 4 (3) ◽  
pp. 359-366 ◽  
Author(s):  
Martin Hergersberg ◽  
Koichi Matsuo ◽  
Max Gassmann ◽  
Walter Schaffner ◽  
Bernhard Lüscher ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Fusion Gene ◽  
Specific Expression ◽  
Tissue Specific ◽  
Tissue Specific Expression

Studies on the expression of an H-2K/human growth hormone fusion gene in giant transgenic mice.

1986 ◽  
Vol 5 (8) ◽  
pp. 1877-1883 ◽  
Author(s):  
D. Morello ◽  
G. Moore ◽  
A.M. Salmon ◽  
M. Yaniv ◽  
C. Babinet
Keyword(s):  
Growth Hormone ◽  
Transgenic Mice ◽  
Human Growth Hormone ◽  
Fusion Gene ◽  
Human Growth

scholarly journals Sex Differences in Estrogen-Dependent Transcription of Gonadotropin-Releasing Hormone (GnRH) Gene Revealed in GnRH Transgenic Mice

Endocrinology ◽  
2003 ◽  
Vol 144 (8) ◽  
pp. 3351-3358 ◽  
Author(s):  
Niren R. Thanky ◽  
Ruth Slater ◽  
Allan E. Herbison
Keyword(s):  
Transgenic Mice ◽  
Mrna Expression ◽  
Gene Transcription ◽  
Transgene Expression ◽  
Gonadal Steroids ◽  
Critical Element ◽  
Sexually Dimorphic ◽  
Mrna Levels ◽  
Estrogen Replacement

Abstract The mechanisms through which gonadal steroids exert feedback actions on the activity of the GnRH neurons are not understood. Using a series of GnRH-LacZ transgenic mice we have examined the manner in which gonadal steroids suppress GnRH mRNA expression in male and female mice. The long-term gonadectomy of 5.5-GNZ-3.5 transgenic mice resulted in significant increases in cellular GnRH mRNA expression (P < 0.05) and plasma LH concentrations (P < 0.01) in both sexes. However, cellular levels of LacZ mRNA and β-galactosidase, which provide an index of GnRH gene transcription, were only elevated in males after gonadectomy. This sexually differentiated response was also observed in mice gonadectomized for 2 wk. Estrogen replacement in gonadectomized males returned transgene expression to intact levels. Experiments in transgenic mice with 3′ and 5′ deleted GnRH-LacZ constructs revealed that the suppressive influence of estrogen on LacZ transcription in the male required a critical element located between −5.2 and −1.7 kb of the GnRH promoter. These studies show that the suppression of GnRH mRNA expression by estrogen in the male involves a decrease in GnRH gene transcription that is dependent on a distal GnRH promoter element. The same mechanism does not exist in females, indicating that gonadal steroids suppress GnRH mRNA levels in a sexually dimorphic manner.

scholarly journals Tissue-specific, developmental, hormonal, and dietary regulation of rat phosphoenolpyruvate carboxykinase-human growth hormone fusion genes in transgenic mice.

1992 ◽  
Vol 12 (3) ◽  
pp. 1007-1020 ◽  
Author(s):  
M K Short ◽  
D E Clouthier ◽  
I M Schaefer ◽  
R E Hammer ◽  
M A Magnuson ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Transgenic Mice ◽  
Human Growth Hormone ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Human Growth ◽  
Fusion Genes ◽  
Specific Expression ◽  
Tissue Specific ◽  
Cis Acting ◽  
Specific Manner

The cytosolic phosphoenolpyruvate carboxykinase (PEPCK) gene is expressed in multiple tissues and is regulated in a complex tissue-specific manner. To map the cis-acting DNA elements that direct this tissue-specific expression, we made transgenic mice containing truncated PEPCK-human growth hormone (hGH) fusion genes. The transgenes contained PEPCK promoter fragments with 5' endpoints at -2088, -888, -600, -402, and -207 bp, while the 3' endpoint was at +69 bp. Immunohistochemical analysis showed that the -2088 transgene was expressed in the correct cell types (hepatocytes, proximal tubular epithelium of the kidney, villar epithelium of the small intestine, epithelium of the colon, smooth muscle of the vagina and lungs, ductal epithelium of the sublingual gland, and white and brown adipocytes). Solution hybridization of hGH mRNA expressed from the transgenes indicated that white and brown fat-specific elements are located distally (-2088 to -888 bp) and that liver-, gut-, and kidney-specific elements are located proximally (-600 to +69 bp). However, elements outside of the region tested are necessary for the correct developmental pattern and level of PEPCK expression in kidney. Both the -2088 and -402 transgenes responded in a tissue-specific manner to dietary stimuli, and the -2088 transgene responded to glucocorticoid stimuli. Thus, different tissues utilize distinct cell-specific cis-acting elements to direct and regulate the PEPCK gene.

scholarly journals Ksp-cadherin gene promoter. II. Kidney-specific activity in transgenic mice

1999 ◽  
Vol 277 (4) ◽  
pp. F599-F610 ◽  
Author(s):  
Peter Igarashi ◽  
Cooduvalli S. Shashikant ◽  
R. Brent Thomson ◽  
Dilys A. Whyte ◽  
Shuxian Liu-Chen ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Transgenic Mice ◽  
Collecting Duct ◽  
Gene Promoter ◽  
Regulatory Elements ◽  
Developmental Expression ◽  
Tubular Epithelial Cells ◽  
Specific Expression ◽  
Tissue Specific

Kidney-specific cadherin (Ksp-cadherin, cadherin 16) is a tissue-specific member of the cadherin superfamily that is expressed exclusively in the basolateral membrane of tubular epithelial cells in the kidney. To determine the basis for tissue-specific expression of Ksp-cadherin in vivo, we evaluated the activity of the promoter in transgenic mice. Transgenic mice containing 3.3 kb of the mouse Ksp-cadherin promoter and an Escherichia coli lacZ reporter gene were generated by pronuclear microinjection. Assays of β-galactosidase enzyme activity showed that the transgene was expressed exclusively in the kidney in both adult and developing mice. Within the kidney, the transgene was expressed in a subset of renal tubular epithelial cells that endogenously expressed Ksp-cadherin and that were identified as collecting ducts by colabeling with Dolichos biflorus agglutinin. In the developing metanephros, expression of the transgene in the branching ureteric bud correlated with the developmental expression of Ksp-cadherin. Identical patterns of expression were observed in multiple founder mice, indicating that kidney specificity was independent of transgene integration site. However, heterocellular expression was observed consistent with repeat-induced gene silencing. We conclude that the Ksp-cadherin gene promoter directs kidney-specific expression in vivo. Regulatory elements that are sufficient to recapitulate the tissue- and differentiation-specific expression of Ksp-cadherin in the renal collecting duct are located within 3.3 kb upstream to the transcriptional start site.

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