Large fragment of the probasin promoter targets high levels of transgene expression to the prostate of transgenic mice

Prostate. 1997 Jul 1;32(2):129-39. doi: 10.1002/(sici)1097-0045(19970701)32:2<129::aid-pros8>;2-h.


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, -11,500 to +28 bp) was isolated, linked to the bacterial chloramphenicol acetyl transferase (CAT) gene, and microinjected into CD1 mouse oocytes to generate 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 1, developmental regulation of LPB-CAT was detected early, from 1 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 returned LPB-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 study demonstrates 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Androgen-Binding Protein / biosynthesis
  • Androgen-Binding Protein / genetics*
  • Animals
  • Chloramphenicol O-Acetyltransferase / biosynthesis
  • DNA Primers
  • Dexamethasone / pharmacology
  • Dihydrotestosterone / pharmacology
  • Epithelium / metabolism
  • Female
  • Gene Expression Regulation, Developmental / drug effects
  • Genes, Reporter
  • Male
  • Mice
  • Mice, Transgenic
  • Oocytes / physiology
  • Orchiectomy
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic*
  • Prostate / growth & development
  • Prostate / metabolism*
  • Rats
  • Transglutaminases / biosynthesis
  • Transglutaminases / genetics
  • Zinc Sulfate / pharmacology


  • Androgen-Binding Protein
  • DNA Primers
  • probasin
  • Dihydrotestosterone
  • Zinc Sulfate
  • Dexamethasone
  • Chloramphenicol O-Acetyltransferase
  • Transglutaminases