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Inhibition of expression of a mouse alpha-globin gene by plasmids that include antisense oligonucleotides.

Identifieur interne : 004724 ( Main/Exploration ); précédent : 004723; suivant : 004725

Inhibition of expression of a mouse alpha-globin gene by plasmids that include antisense oligonucleotides.

Auteurs : K. Yokoyama [Japon] ; D X Hou ; H. Gao ; X. Tang ; I. Kitabayashi ; K. Nishikura ; G. Gachelin

Source :

RBID : pubmed:1295698

Descripteurs français

English descriptors

Abstract

Plasmid-borne DNAs, corresponding to 68-base oligodeoxynucleotides, synthesized in the antisense or sense configuration and based on the nucleotide sequences of various regions of the mouse alpha-globin mRNA, were introduced with the gene for xanthine-guanine phosphoribosyl transferase from E. coli (Ecogpt) into mouse erythroleukemia (MEL) cells by protoplast fusion. Specific inhibition of the synthesis of alpha-globin was observed only in the cells transformed with the plasmids with antisense 68-mers that corresponded to the cap site as well as the site of initiation of translation of alpha-globin mRNA (Oligo-A); Other plasmids with antisense 68-mers that corresponded to the regions of the exon/intron junctions, the individual exons, or the 3' untranslated region were ineffective. This antisense RNA efficiently reduced the production of alpha-globin to 9-18% of the endogenous level after induction with hexylmethylene-bis-acetoamide (HMBA). Moreover, most of the antisense transformants did not show any decrease in the expression of the c-myc gene at the early phases of differentiation of MEL cells. Thus, we propose a hypothesis that the early decline in levels of c-myc mRNA may be independent of and uncoupled from the program of globin synthesis during the differentiation of MEL cells.

DOI: 10.1247/csf.17.433
PubMed: 1295698


Affiliations:


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Le document en format XML

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<term>DNA, Recombinant (genetics)</term>
<term>Gene Expression Regulation (drug effects)</term>
<term>Genes, myc</term>
<term>Globins (biosynthesis)</term>
<term>Globins (genetics)</term>
<term>Leukemia, Erythroblastic, Acute</term>
<term>Mice</term>
<term>Models, Genetic</term>
<term>Molecular Sequence Data</term>
<term>Plasmids</term>
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<term>Coiffes des ARN (génétique)</term>
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<term>Globines (biosynthèse)</term>
<term>Globines (génétique)</term>
<term>Gènes myc</term>
<term>Leucémie érythroblastique aigüe</term>
<term>Modèles génétiques</term>
<term>Plasmides</term>
<term>Régulation de l'expression des gènes ()</term>
<term>Souris</term>
<term>Séquence nucléotidique</term>
<term>Séquences d'acides nucléiques régulatrices</term>
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<front>
<div type="abstract" xml:lang="en">Plasmid-borne DNAs, corresponding to 68-base oligodeoxynucleotides, synthesized in the antisense or sense configuration and based on the nucleotide sequences of various regions of the mouse alpha-globin mRNA, were introduced with the gene for xanthine-guanine phosphoribosyl transferase from E. coli (Ecogpt) into mouse erythroleukemia (MEL) cells by protoplast fusion. Specific inhibition of the synthesis of alpha-globin was observed only in the cells transformed with the plasmids with antisense 68-mers that corresponded to the cap site as well as the site of initiation of translation of alpha-globin mRNA (Oligo-A); Other plasmids with antisense 68-mers that corresponded to the regions of the exon/intron junctions, the individual exons, or the 3' untranslated region were ineffective. This antisense RNA efficiently reduced the production of alpha-globin to 9-18% of the endogenous level after induction with hexylmethylene-bis-acetoamide (HMBA). Moreover, most of the antisense transformants did not show any decrease in the expression of the c-myc gene at the early phases of differentiation of MEL cells. Thus, we propose a hypothesis that the early decline in levels of c-myc mRNA may be independent of and uncoupled from the program of globin synthesis during the differentiation of MEL cells.</div>
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