3' enhancers hs3b/hs4 are dispensable for deregulation in mouse plasmacytomas with T(12;15) translocations.

-deregulating T(12;15) chromosomal translocations are the hallmark cytogenetic abnormalities of murine plasmacytomas (PCTs). In most PCTs, the immunoglobulin heavy chain () locus is broken between the enhancer and the 3' regulatory region (), making the latter the major candidate for orchestrating deregulation. To elucidate the role of the in tumorigenesis, we induced PCTs in transgenic mice deficient for the major enhancer elements, and (hs3b-4). Contrary to previous observations using a mouse lymphoma model, which showed no tumors with peripheral B-cell phenotype in hs3b-4 mice, these animals developed T(12;15)-positive PCTs, although with a lower incidence than hs3b-4 (wild-type, WT) controls. In heterozygous hs3b-4 mice there was no allelic bias in targeting for T(12;15). Molecular analyses of junctions revealed dominance of region breakpoints versus the prevalence of Sγ or Sα in WT controls. expression and Ig secretion in hs3b-4 PCTs did not differ from WT controls. We also evaluated the effect of a complete deletion on expression in the context of an established / translocation in ARS11-transgenic PCT cell lines. Cre-mediated deletion of the resulted in gradual reduction of expression, loss of proliferative activity and increased cell death, confirming the necessity of the for deregulation by T(12;15).