Osteoblast-specific expression of growth hormone stimulates bone growth in transgenic mice

1992 ◽  
Vol 12 (12) ◽  
pp. 5541-5547
Author(s):  
A R Baker ◽  
P G Hollingshead ◽  
S Pitts-Meek ◽  
S Hansen ◽  
R Taylor ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Transgenic Mice ◽  
Bone Growth ◽  
Blot Hybridization ◽  
Postnatal Growth ◽  
Systemic Effects ◽  
Specific Expression ◽  
Important Regulator

Growth hormone (GH) is an important regulator of postnatal growth, acting on a wide variety of target tissues. Here, we show that local production of GH in osteoblasts is able to stimulate bone growth directly without significant systemic effects. Mice were made transgenic by microinjection of an osteocalcin-human GH (osteocalcin-hGH) gene construct in which approximately 1,800 bp of the rat osteocalcin promoter was fused to the hGH gene. Five lines of transgenic mice, each with measurable amounts of serum hGH (ranging from 1 to 1,000 ng/ml), were analyzed. Northern (RNA) blot hybridization showed that the hGH transcript was detectable only in the bone. Further characterization of hGH mRNA distribution by in situ hybridization revealed that in neonates the most intense signal was found in periosteal osteoblasts, while in adults, trabecular and endosteal osteoblasts were favored. In one transgenic line (992-1), hGH was expressed at a much lower level and had minimal systemic effects; however, the local concentrations of hGH in bone were sufficient to stimulate bone growth in these animals.

scholarly journals Osteoblast-specific expression of growth hormone stimulates bone growth in transgenic mice.

1992 ◽  
Vol 12 (12) ◽  
pp. 5541-5547 ◽  
Author(s):  
A R Baker ◽  
P G Hollingshead ◽  
S Pitts-Meek ◽  
S Hansen ◽  
R Taylor ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Transgenic Mice ◽  
Bone Growth ◽  
Blot Hybridization ◽  
Postnatal Growth ◽  
Systemic Effects ◽  
Specific Expression ◽  
Important Regulator

Growth hormone (GH) is an important regulator of postnatal growth, acting on a wide variety of target tissues. Here, we show that local production of GH in osteoblasts is able to stimulate bone growth directly without significant systemic effects. Mice were made transgenic by microinjection of an osteocalcin-human GH (osteocalcin-hGH) gene construct in which approximately 1,800 bp of the rat osteocalcin promoter was fused to the hGH gene. Five lines of transgenic mice, each with measurable amounts of serum hGH (ranging from 1 to 1,000 ng/ml), were analyzed. Northern (RNA) blot hybridization showed that the hGH transcript was detectable only in the bone. Further characterization of hGH mRNA distribution by in situ hybridization revealed that in neonates the most intense signal was found in periosteal osteoblasts, while in adults, trabecular and endosteal osteoblasts were favored. In one transgenic line (992-1), hGH was expressed at a much lower level and had minimal systemic effects; however, the local concentrations of hGH in bone were sufficient to stimulate bone growth in these animals.

scholarly journals Molecular characterization and expression of the stratification-related cytokeratins 4 and 15.

1988 ◽  
Vol 106 (4) ◽  
pp. 1249-1261 ◽  
Author(s):  
R E Leube ◽  
B L Bader ◽  
F X Bosch ◽  
R Zimbelmann ◽  
T Achtstaetter ◽  
...  
Keyword(s):  
Basal Cell ◽  
Blot Hybridization ◽  
Northern Blot Hybridization ◽  
Type I ◽  
Specific Expression ◽  
Genes Encoding ◽  
Cell Layers ◽  
Hybridization In Situ ◽  
Stratified Epithelia

A number of human cytokeratins are expressed during the development of stratified epithelia from one-layered polar epithelia and continue to be expressed in several adult epithelial tissues. For studies of the regulation of the synthesis of stratification-related cytokeratins in internal tissues, we have prepared cDNA and genomic clones encoding cytokeratin 4, as a representative of the basic (type II) cytokeratin subfamily and cytokeratin 15, as representative of the acidic (type I) subfamily, and determined their nucleotide sequences. The specific expression of mRNAs encoding these two polypeptides in certain stratified tissues and cultured cell lines is demonstrated by Northern blot hybridization. Hybridization in situ with antisense riboprobes and/or synthetic oligonucleotides shows the presence of cytokeratin 15 mRNA in all layers of esophagus, whereas cytokeratin 4 mRNA tends to be suprabasally enriched, although to degrees varying in different regions. We conclude that the expression of the genes encoding these stratification-related cytokeratins starts already in the basal cell layer and does not depend on vertical differentiation and detachment from the basal lamina. Our results also show that simple epithelial and stratification-related cytokeratins can be coexpressed in basal cell layers of certain stratified epithelia such as esophagus. Implications of these findings for epithelial differentiation and the formation of squamous cell carcinomas are discussed.

scholarly journals Characterization of transgenic mice with neuron-specific expression of soluble epoxide hydrolase

2009 ◽  
Vol 1291 ◽  
pp. 60-72 ◽  
Author(s):  
Robert A. Bianco ◽  
Khristofor Agassandian ◽  
Martin D. Cassell ◽  
Arthur A. Spector ◽  
Curt D. Sigmund
Keyword(s):  
Transgenic Mice ◽  
Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase ◽  
Specific Expression

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.

Molecular Characterization of the Mouse Tyrosinase Gene:Pigment Cell-Specific Expression in Transgenic Mice

1992 ◽  
Vol 5 (5) ◽  
pp. 295-299 ◽  
Author(s):  
FRIEDRICH BEERMANN ◽  
ERIKA SCHMID ◽  
RUTH GANSS ◽  
GUNTHER SCHUTZ3 ◽  
SIEGFRIED RUPPERT
Keyword(s):  
Transgenic Mice ◽  
Molecular Characterization ◽  
Specific Expression
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