B6.129-Gt(ROSA)26Sor^{tm1(HD*103Q)Xwy}/J

Stock number: 007708
Research areas: Mouse/Human Gene Homologs, Neurobiology Research, Research Tools

Description

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.

Detailed description

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.

Development

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.

Allele

Symbol: Gt(ROSA)26Sor^{tm1(HD*103Q)Xwy}
Name: targeted mutation 1, X William Yang
MGI accession ID: MGI:3583991
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); Inserted expressed sequence; Humanized sequence
Synonyms: mhtt-exon1 (103Q); RosaHD
Marker symbol: Gt(ROSA)26Sor
Marker name: gene trap ROSA 26, Philippe Soriano
Marker synonyms: beta geo; Gtrgeo26; Gtrosa26; R26; ROSA26; SETD5-AS1; Thumpd3as1
Chromosome: 6
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Expressed genes: HTT,huntingtin,human
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.