Preproenkephalin promoter "cassette" confers brain expression and synaptic regulation in transgenic mice

David M. Donovan, Motohide Takemura, Bruce F. O'Hara, Michael T. Brannock, George R. Uhl

Research output: Contribution to journalArticle

Abstract

The preproenkephalin A gene is a neurotransmitter gene whose expression can be modulated "trans-synaptically" by changes in neuronal activity. DNA sequences lying within 200 base pairs of this gene's transcription start site resemble consensus binding sites for several transcription factor families. In nonneuronal cell cultures, this promoter region is sufficient to mediate gene responses to depolarization, phorbol esters, adenylate cyclase, and calcium fluxes. To assess the role that these cis-acting elements could play in preproenkephalin expression and regulation in vivo, the expression of a construct containing this 200-base-pair region fused to the chloramphenicol acetyltransferase gene was examined in transgenic mice. This promoter confers modest expression in brain, adrenal, and small intestine, with substantially higher levels in testis. These elements confer trans-synaptic regulation in two well-studied models of trans-synaptic preproenkephalin upregulation but not in a third system, underscoring the specificity of the regulatory sequence elements implicated in the synaptic regulation of neuronal genes.

Original languageEnglish (US)
Pages (from-to)2345-2349
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number6
Publication statusPublished - 1992

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Keywords

  • Dorsal horn
  • Haloperidol
  • Pain
  • Seizure
  • Striatum

ASJC Scopus subject areas

  • Genetics
  • General

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