Tissue-specific and Developmental Regulation of the Rat Insulin II Gene Enhancer, RIPE3, in Transgenic Mice

The rat insulin II gene enhancer, RIPE3 (−126 to −86), mediates β-islet cell-specific activity in transfection assays. To investigate the in vivo activity of RIPE3, we generated mice carrying a transgene consisting of three copies of RIPE3 linked to a minimal chicken ovalbumin promoter in conjunctio...

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Bibliographic Details
Published in:The Journal of biological chemistry 1997-02, Vol.272 (6), p.3567-3572
Main Authors: Stellrecht, Christine M.M., DeMayo, Franco J., Finegold, Milton J., Tsai, Ming-Jer
Format: Article
Language:English
Subjects:
Animals
Chickens
Enhancer Elements, Genetic - physiology
Growth Hormone - blood
Growth Hormone - genetics
Humans
Insulin - genetics
Islets of Langerhans - metabolism
Mice
Mice, Transgenic
Promoter Regions, Genetic
Radioimmunoassay
Rats
Ribonucleases - metabolism
Tissue Distribution
Transcription, Genetic
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Summary:The rat insulin II gene enhancer, RIPE3 (−126 to −86), mediates β-islet cell-specific activity in transfection assays. To investigate the in vivo activity of RIPE3, we generated mice carrying a transgene consisting of three copies of RIPE3 linked to a minimal chicken ovalbumin promoter in conjunction with sequences encoding the human growth hormone gene. 13 transgenic mice were obtained, 11 of which expressed the transgene, as determined by serum radioimmunoassay for human growth hormone. Expression of the transgene was assessed for cell specificity by immunocytochemistry. The pancreatic islet cells invariably stained for growth hormone, while the acinar and ductal cells did not. Staining of adjacent sections for insulin, glucagon, and somatostatin revealed that growth hormone was expressed in the β-cell in all of the mice analyzed, but in some mice α-cells also contained growth hormone. RNase protection analysis revealed that the tissues that consistently express the transgene in these animals are the pancreas and brain. Developmental analysis revealed that the transgene was expressed in the pancreatic bud at embryonic day 9.5, corresponding to the temporal expression pattern of the insulin gene. These results signify that an element as small as 41 base pairs is capable of regulating pancreatic temporal and spatial gene expression in vivo
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.272.6.3567