Distal regulatory elements from the mouse metallothionein locus stimulate gene expression in transgenic mice

R. D. Palmiter, E. P. Sandgren, D. M. Koeller, R. L. Brinster

Research output: Contribution to journalArticle

193 Scopus citations

Abstract

DNA regions of 10 and 7 kb that flank the mouse metallothionein II (MT- II) and MT-I genes, respectively, were combined with a minimally marked MT-I (MT-I*) gene and tested in transgenic mice. This construct resulted in (i) position-independent expression of MT-I* mRNA and copy number-dependent expression, (ii) levels of hepatic MT-I mRNA per cell per transgene that were about half that derived from endogenous MT-I genes, (iii) appropriate regulation by metals and hormones, and (iv) tissue distribution of transgene mRNA that resembled that of endogenous MT-I mRNA. These features were not observed when MT-I* was tested without the flanking regions. These MT-I flanking sequences also improved the expression of rat growth hormone reporter genes, with or without introns, that were under the control of the MT-I promoter. Moreover, they enhanced expression from two of four heterologous promoters/enhancers that were tested. Deletion analysis indicated that regions known to have DNase I-hypersensitive sites were necessary but not sufficient for high-level expression. These data suggest that the DNA regions flanking the mouse MT-I and MT-II genes have functions like the locus control regions described for other genes.

Original languageEnglish (US)
Pages (from-to)5266-5275
Number of pages10
JournalMolecular and cellular biology
Volume13
Issue number9
DOIs
StatePublished - Jan 1 1993

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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