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：12
页码：4506-4511
DOI：10.1073/pnas.0500830102
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Activation-induced cytidine deaminase (AID) is essential for somatic hypermutations (SHM) and class switch recombination. Overexpression of AID in non-B cells can induce SHM in artificial constructs inserted in various loci in the genome. AID overexpression was thus proposed to introduce mutations in a wide variety of genes with little specificity. We previously showed that AID transgenic mice developed T cell lymphomas in which the variable region {beta} genes of the T cell receptor and c-myc were mutated as frequently as SHM in activated B cells. To understand the target specificity of SHM in AID-expressing T lymphomas, we sequenced six oncogenes (c-myc, pim1, p53, atm, tgfbr-2, and k-ras) and two genes (cd4 and cd5) that are actively transcribed in T lymphomas. SHM was found only in c-myc, pim1, cd4, and cd5, which share the E47 binding motif in the enhancer/promoter. The rest that are not mutated in B cells were not mutated in AID-induced T lymphomas either, although they are transcribed in T and B cells. Comparison of several features of SHM, including selection of targets and mutation distribution, suggests that the regulatory mechanism of SHM is similar between T and B cells. SHM base specificities in the CD4 and CD5 genes were biased to AT, indicating that the preference of target bases of the mutations generated by overexpression of AID is not always GC bases but variable between target genes.
关键词：CD4 and CD5 genes ; E47 binding motif ; T lymphoma
