TY - JOUR
AU - Kaiyi Li, Maricela A. Ramirez, Esmie Rose, Arthur L. Beaudet
AB - We have evaluated the feasibility of using fusion genes to link transcriptional promoters of biomedical interest to reporter genes to screen for pharmacological or genetic regulatory effects. Using gene targeting, we generated two lines of embryonic stem (ES) cells expressing human α-fetoprotein (hAFP) under control of the endogenous promoter for the LDL receptor (LDLR). In one line, hAFP was introduced into the first intron after the translational start codon; in the other, hAFP was positioned in the 3′-untranslated region leaving the potential for expression of LDLR intact. In both lines, an internal ribosome entry site (IRES) was included to facilitate translation. Readily measurable levels of hAFP were found in the medium with both targeted ES cell lines, compared with undetectable levels with the starting cell line. The expectation that the level of hAFP would reflect the steady-state level of mRNA for the fusion transcript and secondarily transcriptional control of LDLR was confirmed by correlating hAFP levels with the abundance of LDLR and fusion transcripts. We also generated mice carrying the LDLR–hAFP fusion in the 3′-untranslated region and these mice produced detectable levels of hAFP in serum. Levels of hAFP in culture medium and in serum were increased by simvastatin, a drug known to up-regulate LDLR. These ES cell clones and mice are suitable for pharmacological and genetic screening to detect effects on expression of LDLR. The data demonstrate the feasibility of using gene fusions to screen for drugs and genetic factors that affect expression of a wide variety of genes of interest. « Previous | Next Article » Table of Contents This Article Hum. Mol. Genet. (2002) 11 (26): 3257-3265. doi: 10.1093/hmg/11.26.3257 » Abstract Free Full Text (HTML) Free Full Text (PDF) Free Classifications Article Services Article metrics Alert me when cited Alert me if corrected Find similar articles Similar articles in Web of Science Similar articles in PubMed Add to my archive Download citation Request Permissions Citing Articles Load citing article information Citing articles via CrossRef Citing articles via Scopus Citing articles via Web of Science Citing articles via Google Scholar Google Scholar Articles by Li, K. Articles by Beaudet, A. L. Search for related content PubMed PubMed citation Articles by Li, K. Articles by Ramirez, M. A. Articles by Rose, E. Articles by Beaudet, A. L. Related Content Load related web page information Share Email this article CiteULike Delicious Facebook Google+ Mendeley Twitter What's this? 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TI - A gene fusion method to screen for regulatory effects on gene expression: application to the LDL receptor
JF - Human Molecular Genetics
DO - 10.1093/hmg/11.26.3257
DA - 2002-12-15
UR - https://www.deepdyve.com/lp/oxford-university-press/a-gene-fusion-method-to-screen-for-regulatory-effects-on-gene-R6E5Js6PTG
SP - 3257
VL - 11
IS - 26
DP - DeepDyve
ER -