A targeting vector was constructed in which the exon encoding the secreted form of the immunoglobulin mu (IgM) heavy chain and its three downstream poly(A) sites were replaced by a cDNA fragment encoding the constant region mu4 exon and the exon encoding the membrane-bound form of IgM. The resultant homozygous mutant mice had B cells that did not secrete IgM, but did express membrane-bound IgM. (J:47425)