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标题：Elucidation of IgH intronic enhancer functions via germ-line deletion
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作者：Thomas Perlot ; Frederick W. Alt ; Craig H. Bassing 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2005
卷号：102
期号：40
页码：14362-14367
DOI：10.1073/pnas.0507090102
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Studies of chimeric mice demonstrated that the core Ig heavy chain (IgH) intronic enhancer (iE{micro}) functions in V(D)J and class switch recombination at the IgH locus. To more fully evaluate the role of this element in these and other processes, we generated mice homozygous for germ-line mutations in which the core sequences of iE{micro} (cE{micro}) were either deleted (cE{micro}{Delta}/{Delta} mice) or replaced with a pgk-NeoR cassette (cE{micro}N/N mice). The cE{micro}{Delta}/{Delta} mice had reduced B cell numbers, in association with impaired D to JH and VH to DJH rearrangement, whereas cE{micro}N/N mice had a complete block in IgH V(D)JH recombination, confirming that additional cis elements cooperate with iE{micro} to enforce D to JH recombination. In addition, developing cE{micro}{Delta}/{Delta} and cE{micro}N/N B lineage cells had correspondingly decreased levels of germ-line transcripts from the JH region of the IgH locus ({micro}0 and I{micro} transcripts); although both had normal levels of germ-line VH transcripts, suggesting that cE{micro} may influence IgH locus V(D)J recombination by influencing accessibility of JH proximal regions of the locus. Consistent with chimera studies, peripheral cE{micro}{Delta}/{Delta} B cells had normal surface Ig and relatively normal class switch recombination. However, cE{micro}{Delta}/{Delta} B cells also had relatively normal somatic hypermutation of their IgH variable region genes, showing unexpectedly that the cE{micro} is not required for this process. The availability of mice with the iE{micro} mutation in their germ line will facilitate future studies to elucidate the roles of iE{micro} in VH(D)JH recombination in the context of IgH chromatin structure and germ-line transcription.
关键词：germ-line transcription ; immunoglobulin heavy chain ; somatic hypermutation ; VDJ recombination ; class switch recombination