Recombination and transcription of the endogenous Ig heavy chain locus is effected by the Ig heavy chain intronic enhancer core region in the absenceof the matrix attachment regions

The intronic Ig heavy chain (IgH) enhancer, which consists of the core enha ncer flanked by 5' and 3' matrix attachment regions, has been implicated in control of IgH locus recombination and transcription. To elucidate the reg ulatory functions of the core enhancer and its associated matrix: attachmen t regions in the endogenous IgH lotus, we have introduced targeted deletion s of these elements, both individually and in combination, into an IgH(a/b) -heterozygous embryonic stem cell line. These embryonic stem cells sere use d to generate chimeric mice by recombination activating gene-2 (Rag-2)-defi cient blastocyst complementation, and the effects of the introduced mutatio ns were assayed in mutant B cells. We find that the core enhancer is necess ary and sufficient to promote normal variable (V), diversity (D), and joini ng (J) segment recombination in developing B lineage cells and IgH locus tr anscription in mature B cells. Surprisingly, the 5' and 3' matrix attachmen t regions were dispensable for these processes.