Primary Identifier | MGI:6158679 | Allele Type | Transgenic |
Attribute String | Inducible, Inserted expressed sequence | Gene | Tg(tetO-DMPK*)A2352Coop |
Strain of Origin | FVB/NJ | Induced With | doxycycline/tetracycline |
Is Recombinase | false | Is Wild Type | false |
molecularNote | The transgene contains a human genomic segment containing exons 11-15 of the DMPK gene with 960 interrupted CTG repeats (CUG>960<) in exon 15 (at the site of the endogenous CTG repeats). These interrupted repeats are generated to contain 20 CTGs separated by five nucleotide spacers. The construct also contains 307 bp of the DMPK 3' flanking region containing the natural polyadenylation signals, and two copies of the cHS4 insulator flanking the 5' and 3' ends of the expression construct to prevent effects of the chromosomal insertion site. This mutant DMPK gene is under the direction of the tetO (tet-responsive element) promoter. The transgene integrated in chromosome 1 (9,622,984-9,660,005) is accompanied by a 37 kb genomic duplication. The integration site is located in the intronic region of 2610203C22Rik. It was also noted at that time that five nucleotide changes are in the transgene compared to the human DMPK sequence. Four of these changes (in intron 11 [CCCTTGGCAgCCCCTCTCGT], intron 14 [CACCCGCCCCgTGCCACCCG], and exon 15 [TTGCCAAACCtGCTTTTTCG and CCCAGCCGGCcCCGCCCGCT]) have no known effect on the Tg. One change, in exon 15 [CCTCGGTATcTATTGT], may affect the binding site for an antisense oligo. Similar to the human gene, it was discovered that two exons in the transgene undergo alternative splicing. |