A B-CELL-DEFICIENT MOUSE BY TARGETED DISRUPTION OF THE MEMBRANE EXON OF THE IMMUNOGLOBULIN MU-CHAIN GENE

OF the various classes of antibodies that B lymphocytes can produce, class M (IgM) is the first to be expressed on the membrane of the developing cells. Pre-B cells, the precursors of B-lymphocytes, produce the heavy chain of IgM (mu-chain), but not light chains 1. Recent data suggest that pre-B cells express mu-chains on the membrane together with the 'surrogate' light chains lambda-5 and VpreB (refs 2-7). This complex could control pre-B-cell differentiation, in particular the rearrangement of the light-chain genes 8. We have now assessed the importance of the membrane form of the mu-chain in B-cell development by generating mice lacking this chain. We disrupted one of the membrane exons of the gene encoding the mu-chain constant region by gene targeting 9 in mouse embryonic stem cells 10. From these cells we derived mice heterozygous or homozygous for the mutation. B-cell development in the heterozygous mice seemed to be normal, but in homozygous animals B cells were absent, their development already being arrested at the stage of pre-B-cell maturation.