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The promoter-containing exon of the Ighg3 (immunoglobulin gamma 3) heavy chain constant region gene segment and ~250 base pairs of downstream sequence were replaced by a ~5 kb segment containing a loxP-flanked neomycin resistance cassette and a pre-rearranged V(D)J region utilizing JH2, followed by germline JH3, JH4, and Emu enhancer (VHDJH2-JH3-Jh4-Emu). The floxed selection cassette was deleted by Cre recombinase. FACS analysis of single-cell suspensions of various lymphatic compartments of homozygous mutant 19 day post coitus (dpc) embryos revealed premature expression of gamma 3 immunoglobulin (IgG3) in B cells of bone marrow, spleen, Peyer's patches, peritoneum, and follicular lymph nodes and virtual absence (<1%) of immunoglobulin mu (IgM) on B cells of all lymphatic tissues, demonstrating near-complete exclusion in cis of IgM expression from the mutant allele. In bone marrow of heterozygous mice, ~25% of B cells express only IgG3, while ~11% express only IgM (from the wild-type allele), suggesting IgG3-expressing B cells outcompete those expressing IgM. (J:266641)