The IgA myeloma W3129 contains a deletion in CH3 which prevents the formation of the membrane form of heavy chain mRNA.

We report here a 54 base pair deletion in the CH3 exon of the alpha gene in the mouse myeloma W3129. This deletion results in a loss of 18 amino acids and a change from a glycine to a serine at position 464. The extent of the deletion was determined by sequencing a portion of CH3 cloned from a variant of W3129, and S1 nuclease protection showed the deletion pre-exists in the parental cell line. The deletion removes the donor splice site normally used in joining CH3 to the alpha membrane (MB) exon when forming MB-specific mRNA. Examination of cytoplasmic RNA by blot hybridization and S1 nuclease protection using MB-specific probes showed a complete lack of membrane mRNA in W3129 and its derivatives. An RNA transcript of unknown origin and function which includes sequences from the CH3-MB intron was seen in W3129 and in J558, an IgA, lambda myeloma with specificity for alpha (1----3) linked dextrans. We discuss the possible influence of the mutation on the W3129 protein. In contrast to the other myelomas studied in this laboratory, light chain loss variants are readily isolated from W3129 and are stable in their production of heavy chain [Dackowski and Morrison (1981) Proc. natn. Acad. Sci. U.S.A. 78, 7091-7095].