Figure 1: Physical map of the sf region, genomic organization of Foxp3 and the sf mutation. | Nature Genetics

Figure 1: Physical map of the sf region, genomic organization of Foxp3 and the sf mutation.

From: Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse

Figure 1

a, The 500-kb sf candidate interval is limited by markers DXCch1 and DXCch2. BAC clones K50, K60, K70, K90 and library ID (in parentheses) are indicated. Computational analysis of this region identified 20 putative genes, including nine known genes (in bold): Tcfe3, Kcnd1, Pim2 and “human CMV-interacting protein”, as well as the mouse orthologs for SYP, LMO6, PLP2, T54 (ref. 15) and CACNA1F (encoding the calcium channel α1 subunit disrupted in congenital stationary night blindness30,31; MIM 310500); and two pseudogenes (on lowest level) related to mouse Smt-3B and Ppia. For the remaining new genes (underlined), corresponding to ESTs and/or GENSCAN predictions, RT–PCR experiments further extended and confirmed transcript structure. The transcriptional orientation of each transcript is indicated by a filled arrowhead. Polymorphic markers are shown in italics. b, Genomic organization of Foxp3 and the sf mutation. Coding exons are shown as filled black boxes, whereas noncoding regions are open boxes. Lines connecting exons indicate splicing events and the observed alternate polyadenylation signal is indicated by the dashed line. Note the two different 5′ noncoding exons (−2a and −2b), separated by 640 bp on the chromosome, both of which splice to a second, common noncoding exon (−1). The putative 5′ end of the most distal non-coding exon, '−2b', located 6.1 kb upstream from the first coding exon corresponds well to a promoter region predicted by GENSCAN. The sf mutation is the result of a 2-bp insertion in exon 8 (indicated below the schematic). Exon 8 was amplified and sequenced directly from genomic DNAs derived from the sf mutant, as well as four inbred (C57BL/6J, 101/Rl, C3Hf/Rl, 129/SvJ) and three wild-derived inbred (CAST/Ei, MOLF/Ei, SPRET/Ei) strains of mice. As expected, the 2-bp insertion was specific for sf mice. The HpaI sites (Hp) used to generate the 30.8-kb Foxp3 transgene, as well as the BstXI sites (Bs) used for Southern-blot analysis are shown. The transgene includes the entire gene as well as 12.5 kb and 2.8 kb of 5′ and 3′ flanking sequence, respectively.

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