Preproenkephalin promoter "cassette" confers brain expression and synaptic regulation in transgenic mice.
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.
Laboratory of Molecular Neurobiology, National Institute on Drug Abuse, Baltimore, MD 21224.
D M
DM
Donovan
M
M
Takemura
B F
BF
O'Hara
M T
MT
Brannock
G R
GR
Uhl
D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004745:Enkephalins / Q000235:genetics*; D015870:Gene Expression; D005786:Gene Expression Regulation; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010433:Pentylenetetrazole; D011401:Promoter Regions, Genetic; D011498:Protein Precursors / Q000235:genetics*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012640:Seizures / Q000503:physiopathology; D013569:Synapses / Q000502:physiology*
D004745:Enkephalins; D009838:Oligodeoxyribonucleotides; D011498:Protein Precursors; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D012313:RNA; D004247:DNA; C033660:preproenkephalin; D015500:Chloramphenicol O-Acetyltransferase; D006220:Haloperidol; D010433:Pentylenetetrazole