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Titolo:
LARGE FRAGMENT OF THE PROBASIN PROMOTER TARGETS HIGH-LEVELS OF TRANSGENE EXPRESSION TO THE PROSTATE OF TRANSGENIC MICE
Autore:
YAN Y; SHEPPARD PC; KASPER S; LIN L; HOARE S; KAPOOR A; DODD JG; DUCKWORTH ML; MATUSIK RJ;
Indirizzi:
VANDERBILT UNIV,SCH MED,DEPT UROL SURG & CELL BIOL,21ST & GARLAND AVENASHVILLE TN 37232 VANDERBILT UNIV,SCH MED,DEPT UROL SURG & CELL BIOL NASHVILLE TN 37232 UNIV MANITOBA,DEPT PHYSIOL WINNIPEG MB CANADA UNIV MANITOBA,DEPT UROL WINNIPEG MB CANADA
Titolo Testata:
The Prostate
fascicolo: 2, volume: 32, anno: 1997,
pagine: 129 - 139
SICI:
0270-4137(1997)32:2<129:LFOTPP>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
CHROMATIN STRUCTURE; ANDROGEN REGULATION; GENE-EXPRESSION; FUSION GENE; RAT DORSAL; MOUSE; TUMOR; INDUCTION; POSITION; INTRONS;
Keywords:
PROBASIN; PROSTATE SPECIFIC; TRANSGENIC MICE; ANDROGEN REGULATION; EPITHELIAL CELLS; PROSTATE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
39
Recensione:
Indirizzi per estratti:
Citazione:
Y. Yan et al., "LARGE FRAGMENT OF THE PROBASIN PROMOTER TARGETS HIGH-LEVELS OF TRANSGENE EXPRESSION TO THE PROSTATE OF TRANSGENIC MICE", The Prostate, 32(2), 1997, pp. 129-139

Abstract

BACKGROUND. Androgen regulation and prostate-specific expression of targeted genes in transgenic mice can be controlled by a small DNA fragment of the probasin (PB) promoter (-426 to +28 base pairs, bp). Although the small PB fragment was sufficient to direct prostate-specific expression, the low levels of transgene expression suggested that important upstream regulatory sequences were missing. METHODS. To enhance transgene expression, a large fragment of the PB promoter (LPB, -11,500to +28 bp) was isolated, linked to the bacterial chloramphenicol acetyl transferase (CAT) gene, and microinjected into CD1 mouse oocytes togenerate transgenic mouse lines. RESULTS. As shown by the immunohistochemical studies, CAT gene expression was restricted to the prostatic epithelial cells in a tissue-specific manner. High levels of CAT gene expression were observed in two of the six LPB-CAT transgenic Lines. In Line I, developmental regulation of LPB-CAT was detected early, from1 to 4 weeks of age, with the activity of CAT increasing from 3 to 40,936 dpm/min/mg protein. Upon sexual maturation and elevated serum androgen levels (7 weeks of age), a further 18-fold rise in CAT activity occurred. Hormone ablation by castration in mature mice dramatically reduced transgene expression, whereas treatment with androgens returnedLPB-CAT expression to precastration levels. In contrast, treatment with glucocorticoids had no significant effect on CAT gene expression. Zinc treatment of the castrated animals also increased LPB-CAT expression three- to four-fold in two prostatic lobes. CONCLUSIONS. This studydemonstrates that important regulatory DNA sequences located in the LPB fragment contribute to tissue-specific expression and greatly increase levels of transgene expression induced by androgens and zinc. (C) 1997 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/07/20 alle ore 07:35:26