First Author | Terauchi A | Year | 2001 |
Journal | J Immunol | Volume | 167 |
Issue | 2 | Pages | 811-20 |
PubMed ID | 11441087 | Mgi Jnum | J:132590 |
Mgi Id | MGI:3776336 | Doi | 10.4049/jimmunol.167.2.811 |
Citation | Terauchi A, et al. (2001) A pivotal role for DNase I-sensitive regions 3b and/or 4 in the induction of somatic hypermutation of IgH genes. J Immunol 167(2):811-20 |
abstractText | 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. |