Linked Life Data

9495255

Source:http://linkedlifedata.com/resource/pubmed/id/9495255

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1998-3-19
pubmed:abstractText
Previous researchers have identified two sequences present upstream (angiotensinogen gene-activating element [AGE2]) and downstream (d61-2) of the human angiotensinogen gene that act as cell-specific enhancers of transcription in transiently transfected HepG2 cells. To examine the importance of these two sequences in regulating tissue- and cell-specific expression of the gene in vivo, we generated transgenic mice containing the mutations in the context of a genomic transgene previously shown to exhibit appropriate tissue and cell specificity. The ability of these sequences to enhance transcription of a basal human angiotensinogen promoter was confirmed in transient transfection assays in HepG2 cells, and mutations within the AGE2 and d61-2 sequences abolished transactivation of the promoter. Tissue- and cell-specific expression was examined in three lines of transgenic mice carrying the d61-2 mutation, two lines of transgenic mice carrying the AGE2 mutation, and three founder transgenic mice carrying a double-mutant construct. Although the absolute levels of expression varied among lines, the pattern of tissue-specific expression was essentially unaltered by the mutations. In situ hybridization confirmed that the mutations were also dispensable for proximal tubule-specific expression within the kidney. Finally, a comparison of transgene expression with transgene copy number revealed a direct proportionality in liver (R=.77, P=.0014) and kidney (R=.76, P=.0024). These results clearly demonstrate that these sites, which strongly induce promoter activity in cells in culture, are not required for appropriate expression of the gene when present in a genomic construct in vivo.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0194-911X
pubmed:author
pubmed:issnType
Print
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
734-40
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Regulatory elements required for human angiotensinogen expression in HepG2 cells are dispensable in transgenic mice.
pubmed:affiliation
Department of Anatomy, The University of Iowa College of Medicine, Iowa City 52242, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't