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Trans-splicing as a possible molecular mechanism for the multiple isotype expression of the immunoglobulin gene
We analyzed the molecular mechanism for the immunoglobulin (Ig) multiple isotype expression using a transgenic mouse (TG.SA) model system. Though most of the endogenous mu chain expression was excluded by the expression of the human rearranged mu transgene in the TG.SA mouse, a significant portion o...
Formato: | Texto |
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Lenguaje: | English |
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The Rockefeller University Press
1991
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2190851/ https://www.ncbi.nlm.nih.gov/pubmed/1903429 |
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collection | PubMed |
description | We analyzed the molecular mechanism for the immunoglobulin (Ig) multiple isotype expression using a transgenic mouse (TG.SA) model system. Though most of the endogenous mu chain expression was excluded by the expression of the human rearranged mu transgene in the TG.SA mouse, a significant portion of splenic B lymphocytes could express the transgenic human IgM and endogenous mouse IgG simultaneously after stimulation with lipopolysaccharide and interleukin 4. The fluorescence- activated cell sorter-purified population of the human IgM+/mouse IgG+ cells expressed mRNA that consisted of properly spliced sequences of the transgenic VHDJH and the endogenous mouse C gamma genes (trans- mRNA), together with the transgenic human mu mRNA and germline transcripts of the mouse C gamma gene, without apparent rearrangement of the transgene. We also found that a lymphoma tumor, derived from the cross between the TG.SA mouse and another transgenic mouse carrying Ig H chain enhancer-driven c-myc oncogene, expressed about equal levels of the trans-mRNA and the transgenic mu mRNA without DNA rearrangement in either the transgene or the endogenous mouse switch region. These findings strongly support our previous proposal that the trans-splicing can account for the multiple isotype expression in this transgenic model and also suggest that novel molecular mechanism(s) might be involved in this reaction. |
format | Text |
id | pubmed-2190851 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1991 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21908512008-04-17 Trans-splicing as a possible molecular mechanism for the multiple isotype expression of the immunoglobulin gene J Exp Med Articles We analyzed the molecular mechanism for the immunoglobulin (Ig) multiple isotype expression using a transgenic mouse (TG.SA) model system. Though most of the endogenous mu chain expression was excluded by the expression of the human rearranged mu transgene in the TG.SA mouse, a significant portion of splenic B lymphocytes could express the transgenic human IgM and endogenous mouse IgG simultaneously after stimulation with lipopolysaccharide and interleukin 4. The fluorescence- activated cell sorter-purified population of the human IgM+/mouse IgG+ cells expressed mRNA that consisted of properly spliced sequences of the transgenic VHDJH and the endogenous mouse C gamma genes (trans- mRNA), together with the transgenic human mu mRNA and germline transcripts of the mouse C gamma gene, without apparent rearrangement of the transgene. We also found that a lymphoma tumor, derived from the cross between the TG.SA mouse and another transgenic mouse carrying Ig H chain enhancer-driven c-myc oncogene, expressed about equal levels of the trans-mRNA and the transgenic mu mRNA without DNA rearrangement in either the transgene or the endogenous mouse switch region. These findings strongly support our previous proposal that the trans-splicing can account for the multiple isotype expression in this transgenic model and also suggest that novel molecular mechanism(s) might be involved in this reaction. The Rockefeller University Press 1991-06-01 /pmc/articles/PMC2190851/ /pubmed/1903429 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Articles Trans-splicing as a possible molecular mechanism for the multiple isotype expression of the immunoglobulin gene |
title | Trans-splicing as a possible molecular mechanism for the multiple isotype expression of the immunoglobulin gene |
title_full | Trans-splicing as a possible molecular mechanism for the multiple isotype expression of the immunoglobulin gene |
title_fullStr | Trans-splicing as a possible molecular mechanism for the multiple isotype expression of the immunoglobulin gene |
title_full_unstemmed | Trans-splicing as a possible molecular mechanism for the multiple isotype expression of the immunoglobulin gene |
title_short | Trans-splicing as a possible molecular mechanism for the multiple isotype expression of the immunoglobulin gene |
title_sort | trans-splicing as a possible molecular mechanism for the multiple isotype expression of the immunoglobulin gene |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2190851/ https://www.ncbi.nlm.nih.gov/pubmed/1903429 |