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J Immunol. 2001 Jul 15;167(2):811-20.

A pivotal role for DNase I-sensitive regions 3b and/or 4 in the induction of somatic hypermutation of IgH genes.

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Division of Biosignaling, Research Institute for Biological Sciences, Science University of Tokyo, Yamazaki 2669, Noda, Chiba 278 0022, Japan.


Chimeric mice were prepared from embryonic stem cells transfected with IgH genes as transgenes and RAG-2-deficient blastocysts for the purpose of identifying the cis-acting elements responsible for the induction of somatic hypermutation. Among the three transgene constructs used, the V(H) promoter, the rearranged V(H)-D-J(H), an intron enhancer/matrix attachment region, and human Cmu were common to all, but the 3'-untranslated region in each construct was different. After immunization of mice with a T cell-dependent Ag, the distribution and frequency of hypermutation in transgenes were analyzed. The transgene lacking the 3' untranslated region showed a marginal degree of hypermutation. Addition of the 3' enhancer resulted in a slight increase in the number of mutations. However, the transgene containing DNase I-sensitive regions 3b and 4 in addition to the 3' enhancer showed more than a 10-fold increase in hypermutation, reaching levels comparable to those observed in endogenous V(H)186.2 genes of C57BL/6 mice.

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