Figure 1: Transgene rearrangement and insertion into the mouse genome.

(a) The original structure of the R6 transgene (top schematic, drawn to scale) and its extensive resultant rearrangement following integration into chromosome 4 of the R6/2 mouse (bottom schematic) are shown. The R6/2 integrated transgene contained fragments derived from at least three copies of the original R6 transgene, including complex inversions as well as head-to-tail and tail-to-head concatenations. Additionally, a 168 bp fragment of bacterial sequence was integrated upstream of the transgene HTT 5′ genomic sequence². (b) Integration of a 1.9 kb HTT transgene fragment into intron 7 of mouse locus Gm12695 and concomitant 5.4 kb deletion of intron 7 at the integration site (demarcated by dotted lines). PhyloP³⁸ analysis of mammalian conservation spanning the gene is provided, revealing the deleted intronic segment to be among the most conserved regions in the gene, including its coding sequence.