These RosaHD mutant mice allow cre-conditional expression of the neuropathogenic mhtt-exon1 protein and may be useful in studying Huntington’s disease or other polyQ disorders.
X. William Yang, University of California Los Angeles
Mice heterozygous for the RosaHD mutant allele are viable and fertile. These mice have the neuropathogenic polyQ-mutant variant of the human Huntingtin protein (mhtt-exon1; 103Q) inserted into the Gt(ROSA)26Sor locus. Expression of mhtt-exon1 is blocked by an upstream loxP-flanked transcriptional STOP sequence. When bred to mice with a Cre recombinase gene under the control of a promoter of interest, the STOP sequence is deleted in the tissue of interest, and mhtt-exon1 expression is observed. As these RosaHD mutant mice allow cre-conditional expression of the neuropathogenic mhtt-exon1 protein, they may be useful in studying Huntington's disease (HD) or other polyQ disorders. Of note, sequencing of the polyQ region (using mice from the 11th backcross) indicate the actual number of repeats to be 98.
For example, when bred to strains expressing cre in brain tissues (such as Nestin-Cre (see Stock No. 003771) or Emx1-Cre (see Stock No. 005628), bi-transgenic offspring show pathological cell-cell interactions critically contribute to cortical pathogenesis of HD.
A targeting vector was designed with a loxP-flanked transcriptional STOP sequence immediately upstream of a polyQ-mutant form of the human Huntingtin protein exon 1 (mhtt-exon1) sequence (containing 103 mixed CAA-CAG repeats, each encoding glutamine), all followed by a polyadenylation sequence. This targeting construct was incorporated into the Gt(ROSA)26Sor locus via electroporation into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were microinjected into C57BL/6J blastocysts. The resulting "RosaHD" mutant mice were subsequently backcrossed to C57BL/6J mice for at least 11 generations prior to arrival at The Jackson Laboratory. Of note, sequencing of the polyQ region (using mice from the 11th backcross) indicate the actual number of repeats to be 98.
|Expressed Gene||HTT, huntingtin, human|
|Site of Expression|
|Allele Name||targeted mutation 1, X William Yang|
|Allele Type||Targeted (Conditional ready (e.g. floxed), Humanized sequence, Inserted expressed sequence)|
|Allele Synonym(s)||RosaHD; mhtt-exon1 (103Q)|
|Gene Symbol and Name||Gt(ROSA)26Sor, gene trap ROSA 26, Philippe Soriano|
|Gene Synonym(s)||AV258896; Gtrgeo26; Gtrgeo26; Gtrosa26; Gtrosa26; R26; ROSA26; SETD5-AS1; Thumpd3as1; beta geo; expressed sequence AV258896; gene trap ROSA 26; gene trap ROSA b-geo 26|
|Expressed Gene||HTT, huntingtin, human|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl<+>|
|Molecular Note||A targeting vector was designed with a loxP-flanked transcriptional STOP sequence immediately upstream of a neuropathogenic polyQ-mutant form of the human Huntingtin protein exon 1 (mhtt-exon1) sequence (containing 103 mixed CAA-CAG repeats, each encoding glutamine), all followed by a polyadenylation sequence. When these mice are bred with animals expressing cre under the control of a promoter of interest, The STOP signal is deleted in tissue of interest allowing conditional expression of mhtt1-exon1.|
When maintaining a live colony, heterozygous mice may be bred to wildtype siblings or to C57BL/6J inbred mice. While presumed to be viable and fertile, the phenotype of homozygous mice has not been reported (Aug-2007).
When using the B6.129-Gt(ROSA)26Sortm1(HD*103Q)Xwy/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #007708 in your Materials and Methods section.
|Heterozygous or Wild-type for Gt(ROSA)26Sor<tm1(HD*103Q)Xwy>|
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