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

Richard D. Palmiter, Eric P. Sandgren, David Koeller, Ralph L. Brinster

Research output: Contribution to journalArticle

192 Citations (Scopus)

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
StatePublished - Sep 1993
Externally publishedYes

Fingerprint

Metallothionein
Transgenic Mice
Gene Expression
Messenger RNA
Genes
Transgenes
Locus Control Region
Deoxyribonuclease I
DNA
Tissue Distribution
Reporter Genes
Introns
Growth Hormone
Metals
Hormones
Liver

ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology

Cite this

Distal regulatory elements from the mouse metallothionein locus stimulate gene expression in transgenic mice. / Palmiter, Richard D.; Sandgren, Eric P.; Koeller, David; Brinster, Ralph L.

In: Molecular and Cellular Biology, Vol. 13, No. 9, 09.1993, p. 5266-5275.

Research output: Contribution to journalArticle

Palmiter, Richard D. ; Sandgren, Eric P. ; Koeller, David ; Brinster, Ralph L. / Distal regulatory elements from the mouse metallothionein locus stimulate gene expression in transgenic mice. In: Molecular and Cellular Biology. 1993 ; Vol. 13, No. 9. pp. 5266-5275.
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