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International Immunology Advance Access originally published online on February 28, 2006
International Immunology 2006 18(4):581-589; doi:10.1093/intimm/dxh400
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© The Japanese Society for Immunology. 2006. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Germ line transcription in mice bearing neor gene downstream of I{gamma}3 exon in the Ig heavy chain locus

Maha Samara1,2, Zeliha Oruc1, Hei-Lanne Dougier1, Tamer Essawi2, Michel Cogné3 and Ahmed Amine Khamlichi1,4

1 CNRS UMR 6101, Groupe ‘Instabilité génétique et régulation transcriptionnelle’, Faculté de Médecine, 2 rue du Dr Marcland, F-87025 Limoges cedex, France
2 Department of Clinical Sciences, Birzeit University, Birzeit, Palestine
3 CNRS UMR 6101, Groupe ‘Génétique moléculaire de la cellule B et des syndromes immunoprolifératifs’, Faculté de Médecine, Limoges, France
4 Present address: CNRS UMR 5089-IPBS, Equipe "Instabilité génétique et régulation transcriptionnelle", 205 route de Narbonne, 31077 Toulouse cedex 4, France

Correspondence to: A. A. Khamlichi; E-mail: ahmed.khamlichi{at}unilim.fr

Class switch recombination (CSR) is preceded by germ line transcription that initiates from promoters upstream of switch (S) sequences and terminates downstream of associated constant genes. Previous work showed that germ line transcripts and their processing are required for CSR and that germ line transcription is regulated in a major part by a regulatory region located downstream of the Ig heavy chain locus. This long-range, polarized effect can be disturbed by inserting an expressed neomycine resistance (neor) gene. To contribute to a better understanding of the mechanism of such a long-distance regulation, we generated knock-in mice in which a neor gene was inserted downstream of I{gamma}3 exon leaving intact all the necessary elements for germ line transcription and splicing. We show that the expressed neor gene interferes with transcription initiation from I{gamma}3, and that it impairs but does not block S recombination to C{gamma}3. Moreover, we show for the first time that the neor gene provides through chimeric neor-C{gamma}3 transcripts the necessary elements for splicing of germ line transcripts by activating two novel cryptic splice sites, one in the coding region of the intronless neor gene and the other in the I{gamma}3-C{gamma}3 intron.

Keywords: B lymphocyte, class switch recombination, long-range interaction, splicing

Transmitting editor: A. Radbruch


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Proc. Natl. Acad. Sci. USAHome page
Z. Oruc, A. Boumediene, M. Le Bert, and A. A. Khamlichi
Replacement of I{gamma}3 germ-line promoter by I{gamma}1 inhibits class-switch recombination to IgG3
PNAS, December 18, 2007; 104(51): 20484 - 20489.
[Abstract] [Full Text] [PDF]



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