B-cell specific deletion of the 13q14-CDR in mice. (A) Schematic representation of the human 13q14 and mouse 14qC3 locus. Genes and their 5′-3′ orientation are indicated by thick arrows. The deleted regions in the MDR and miR-15a/16-1 mouse models described previously²²  are indicated. Because in humans, KCNRG is encoded within an intron of DLEU2, the former gene is considered part of the human MDR. In mice, and in contrast to what is found in humans, dleu2, in addition to Kcnrg, also overlaps with dleu5 (exon 3 of dleu5 is located in the last intron of dleu2), thus making dleu5 part of the mouse MDR. (B) Schematic representation of the CDR targeting strategy (for details, see supplemental Figure 1-A1 to A4). Indicated are the expected fragments detected by Southern blot analysis after Flp-mediated recombination in mice, which generates an CDR-null allele, and after Adeno-Cre–mediated recombination in CDR^fl/+ ES cells, which shows a ΔloxP fragment in addition to the targeted fragment, demonstrating the feasibility of deleting the 0.8-mb conditional CDR allele. Flow cytometric analysis of Adeno-Cre–treated CDR^fl/+ ES cells shows that deletion of the CDR is accompanied by eGFP expression (for details, see supplemental Figures 1-2). (C) Deletion of the 0.8-mb loxP-flanked CDR allele in vivo. Southern blot analysis of SpeI-digested DNA from purified CD19⁺ B cells of CDR^fl/+CD19-Cre and CDR^fl/+ mice. CDR^fl/+CD19-Cre mice show the WT allele and the allele after loxP-mediated deletion.