Map of LCR deletions obtained by homologous recombination and the expression analysis of the resulting mutant mice. (A) Map of the mouse β-globin locus. Blocks with arrowheads represent genes. Vertical arrows represent LCR HSs. (B) Diagrammatic representation of the targeted deletions generated and discussed in the text. Each block demonstrates the extent of the deletion listed on the left of the panel. Note that the Δ1-2 and Δ2-3 deletions remove all sequences from the 5′ border to the 3′ border of the corresponding single HS deletions, thus removing sequences between the 2 HSs. In contrast, the Δ1,4 deletion only removes the sequences present in the 2 single HS deletions. (C) Adult β-globin expression resulting from LCR HS deletions. The level of expression from a mutant allele relative to that of a WT allele in heterozygotic mice is presented as a percentage with the SD denoted (see “The β-globin LCR HSs contribute to transcription in an addictive, not synergistic manner” and Table 1 for details). Black bars are data from tissue RNA preparations and light bars are data from single-cell analyses. (D) Deficit in adult β-globin expression resulting from LCR HS deletions. The deficit in expression of a mutant allele compared with a WT allele in heterozygotic mice was calculated by subtracting the expression level (Figure 1C) from 100% and is presented with the SD (see “The β-globin LCR HSs contribute to transcription in an addictive, not synergistic manner” and Table 2 for details). Striped bars are the calculated deficit that would be observed in double HS deletion mice if HSs contribute to expression in an additive manner. Black bars are data from tissue RNA preparations and light bars are data from single-cell analyses.