Igh^tm1.1Rsky

A DNA segment containing a IgH-6 gene (heavy chain of IgM) and an inverted Ighg1 (heavy constant gamma 1 chain) was inserted immediately downstream of the constant heavy chain gene region (CH). To restrict expression of soluble isoforms, the relevant polyA sites were mutated (Ighg1) or eliminated (Igh-6). LoxP sites in opposite orientations were placed around the genes and a neomycin resistance cassette was placed upstream of the entire construct. This construct was used in targeting of stem cells from Igh-6tm1Fbb mice in which the Igh-6 locus is replaced with a loxP site. Chimeric mice were crossed with transgenic mice expressing Cre recombinase, eliminating the entire CH region and the neo resistance cassette while leaving the mutant IgH-6 gene intact and in the right orientation to express. B cells from these mice were confirmed to exclusively express membrane bound IgM antibody. (J:125719)