Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2000-12-11
pubmed:abstractText
The c-fes proto-oncogene encodes a 92-kd protein tyrosine kinase whose expression is restricted largely to myeloid and endothelial cells in adult mammals. A 13.2-kilobase (kb) human c-fes genomic fragment was previously shown to contain cis-acting element(s) sufficient for a locus control function in bone marrow macrophages. Locus control regions (LCRs) confer transgene expression in mice that is integration site independent, copy number dependent, and similar to endogenous murine messenger RNA levels. To identify sequences required for this LCR, c-fes transgenes were analyzed in mice. Myeloid-cell-specific, deoxyribonuclease-I-hypersensitive sites localized to the 3' boundary of exon 1 and intron 3 are required to confer high-level transgene expression comparable to endogenous c-fes, independent of integration site. We define a minimal LCR element as DNA sequences (nucleotides +28 to +2523 relative to the transcription start site) located within intron 1 to intron 3 of the human locus. When this 2.5-kb DNA fragment was linked to a c-fes complementary DNA regulated by its own 446-base-pair promoter, integration-site-independent, copy-number-dependent transcription was observed in myeloid cells in transgenic mice. Furthermore, this 2.5-kb cassette directed expression of a heterologous gene (enhanced green fluorescent protein) exclusively in myeloid cells. The c-fes regulatory unit represents a novel reagent for targeting gene expression to macrophages and neutrophils in transgenic mice.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
96
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3040-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11049982-Animals, pubmed-meshheading:11049982-Bone Marrow Cells, pubmed-meshheading:11049982-Deoxyribonuclease I, pubmed-meshheading:11049982-Exons, pubmed-meshheading:11049982-Gene Transfer Techniques, pubmed-meshheading:11049982-Genes, Reporter, pubmed-meshheading:11049982-Green Fluorescent Proteins, pubmed-meshheading:11049982-Humans, pubmed-meshheading:11049982-Locus Control Region, pubmed-meshheading:11049982-Luminescent Proteins, pubmed-meshheading:11049982-Mice, pubmed-meshheading:11049982-Mice, Transgenic, pubmed-meshheading:11049982-Protein-Tyrosine Kinases, pubmed-meshheading:11049982-Proto-Oncogene Proteins, pubmed-meshheading:11049982-Proto-Oncogene Proteins c-fes, pubmed-meshheading:11049982-Proto-Oncogenes, pubmed-meshheading:11049982-RNA, Messenger, pubmed-meshheading:11049982-Spleen, pubmed-meshheading:11049982-Thymus Gland
pubmed:year
2000
pubmed:articleTitle
A minimal c-fes cassette directs myeloid-specific expression in transgenic mice.
pubmed:affiliation
Departments of Molecular Genetics and Cell Biology and Medicine, Howard Hughes Medical Institute, University of Chicago, Chicago, IL, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't