Cell-specific expression from the human dopamine beta-hydroxylase promoter in transgenic mice is controlled via a combination of positive and negative regulatory elements.
The promoter region of the human dopamine beta-hydroxylase (DBH) gene was analyzed in transgenic mice to identify DNA sequences responsible for the tissue- and cell-specific expression of the gene. Transgenic mice were generated that carried the Escherichia coli lacZ gene under control of DBH promoter fragments between 0.6 and 5.8 kilobases (kb) in length. Sequences required for expression in adult and fetal noradrenergic neurons were located between 0.6 and 1.1 kb 5' to the DBH transcriptional start site. Sequences in this region and farther upstream also directed expression to dopaminergic and noncatecholaminergic brain neurons that was repressed by negative elements elsewhere in the gene. The results indicate that the neuron-specific expression of the DBH gene is mediated by positive regulatory elements but that negative elements are required to restrict expression to the proper subset of neurons.
Hoyle
G W
GW
Laboratory of Reproductive Physiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104.
Mercer
E H
EH
Palmiter
R D
RD
Brinster
R L
RL
D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004299:Dopamine beta-Hydroxylase / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics*; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D005724:Ganglia / Q000166:cytology / Q000378:metabolism*; D015870:Gene Expression; D005798:Genes, Bacterial; D005809:Genes, Regulator; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D014158:Transcription, Genetic; D001616:beta-Galactosidase / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics
D004247:DNA; D004299:Dopamine beta-Hydroxylase; D001616:beta-Galactosidase