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    Ialpha exon-replacement mice synthesize a spliced HPRT-C(alpha) transcript which may explain their ability to switch to IgA. Inhibition of switching to IgG in these mice

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    Authors
    Qiu, G.
    Harriman, G. R.
    Stavnezer, Janet
    UMass Chan Affiliations
    Department of Molecular Genetics and Microbiology
    Document Type
    Journal Article
    Publication Date
    1999-01-01
    Keywords
    Animals
    Exons
    Gene Expression Regulation
    Germ Cells
    Hypoxanthine Phosphoribosyltransferase
    Immunoglobulin A
    *Immunoglobulin Class Switching
    Immunoglobulin G
    Immunoglobulin Heavy Chains
    Mice
    Mice, Knockout
    *RNA Splicing
    Recombination, Genetic
    Sequence Analysis, DNA
    Life Sciences
    Medicine and Health Sciences
    Women's Studies
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    Link to Full Text
    http://intimm.oxfordjournals.org/content/11/1/37.full.pdf+html
    Abstract
    Antibody class switching is regulated by transcription of unrearranged C(H) genes to produce germline (GL) transcripts which direct the choice of isotype and are required for switching. However, their role is unknown. GL transcripts are initiated at the I exons located upstream of each switch region. Although deletion of the I exon by gene targeting prevents switch recombination to that CH gene, the Ialpha exon can be replaced by an entirely different DNA segment, a minigene driven by the phosphoglycerate kinase (PGK) promoter and encoding hypoxanthine phosphoribosyl transferase (HPRT), oriented in the sense direction, without reducing antibody class switching to IgA. To understand why HPRT substitution of the Ialpha exon does not disrupt switch recombination, we have analyzed the structure of the transcript from the targeted allele in these mice. We identify a spliced transcript in which the HPRT exons are spliced to the C(alpha) gene segments, resulting in a structure similar to normal GL transcripts. The abundance of this transcript is similar to that of the normal alpha GL RNA. We also demonstrate that switching to the four IgG subclasses in B cells from these mice is reduced in comparison to wild-type mice. We discuss the possibility that the strong PGK promoter inserted at the Ig alpha locus may interfere with interaction of the promoters for gamma GL transcripts with the 3' IgH enhancer.
    Source
    Int Immunol. 1999 Jan;11(1):37-46.
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/50671
    PubMed ID
    10050672
    Related Resources
    Link to article in PubMed
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    UMass Chan Faculty and Researcher Publications

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