The rat probasin gene promoter directs hormonally and developmentally regulated expression of a heterologous gene specifically to the prostate in transgenic mice
| Autor: | Russell M. Lebovitz, Norman M. Greenberg, M. L. Duckworth, Janice G. Dodd, Patricia C. Sheppard, Jeffrey M. Rosen, Roberto Barrios, Milton J. Finegold, Robert J. Matusik, Francesco J. DeMayo, R. Angelopoulou |
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| Rok vydání: | 1994 |
| Předmět: |
Genetically modified mouse
Chloramphenicol O-Acetyltransferase Male Transgene Molecular Sequence Data Mice Transgenic Biology Androgen-Binding Protein Epithelium Chloramphenicol acetyltransferase Mice Endocrinology Prostate Gene expression medicine Animals Cloning Molecular Promoter Regions Genetic Molecular Biology Gene Base Sequence Promoter General Medicine Molecular biology Rats medicine.anatomical_structure Gene Expression Regulation Expression cassette |
| Zdroj: | Molecular endocrinology (Baltimore, Md.). 8(2) |
| ISSN: | 0888-8809 |
| Popis: | An expression cassette carrying 426 basepairs of the rat probasin (PB) gene promoter and 28 basepairs of 5'-untranslated region is sufficient to target the expression of the bacterial chloramphenicol acetyltransferase (CAT) gene specifically to the prostate in transgenic mice. The PB-CAT transgene was expressed in three of five (60%) independent lines of mice, and this expression, as reported previously for the endogenous rat gene, was male specific, restricted primarily to the lateral, dorsal, and ventral lobes of the prostate, with only very low levels of CAT activity detected in the anterior prostate and seminal vesicles. The developmental and hormonal regulation of the transgene also paralleled that reported for the rat gene, with a 70-fold increase in CAT activity in the mouse prostate observed between 2-7 weeks of age, a time corresponding to sexual maturation. PB-CAT activity in the prostate declined after castration to 3.5% of the precastration level, and the CAT activity in castrated males approached precastration levels when mice were supplemented with testosterone. Transgene expression in castrated males was not induced by dexamethasone. Coinjection of PB-CAT with a chicken lysozyme gene matrix attachment region resulted in their cointegration and further restricted the pattern of PB-CAT to the dorsolateral prostate, with suppressed expression observed in the ventral prostate. These studies demonstrate that a minimal rat probasin promoter can target heterologous gene expression specifically to the prostate in a developmentally and hormonally regulated fashion. |
| Databáze: | OpenAIRE |
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