NOD.B6-Gt(ROSA)26Sor^{tm1(HBEGF)Awai}/DvsJ

Stock number: 016603
Product name: NOD.ROSA-DTR
Strain synonyms: ROSA26iDTR
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

The Cre-inducible expression of DTR in these iDTR mutant mice render cells susceptible to ablation following Diphtheria toxin administration.

Detailed description

Mice homozygous for this iDTR mutation are viable and fertile. These mice have the simian Diphtheria Toxin Receptor (DTR; from simian Hbegf) inserted into the Gt(ROSA)26Sor (ROSA26) locus. Widespread expression of DTR is blocked by an upstream loxP-flanked STOP sequence. When bred to Cre recombinase-expressing mice, the STOP sequence is deleted in tissues where Cre is present, permitting DTR expression. Cells expressing DTR are rendered susceptible to ablation following Diphtheria toxin administration.
For instance, the role of a particular cell population in T1D development can be determined by injecting Diphtheria toxin to deplete the specific cells in a timely fashion.

For example, when bred to a strain expressing Cre recombinase in dendritic cells (see Stock No. 013233 for example), this mutant mouse strain may be useful for studies involving the immunology of diabetes.

When crossed to a strain expressing Cre recombinase in T-lymphocytes (see Stock No. 008694), this mutant mouse strain may be useful in studies of regulatory T cell ablation.

Development

A targeting vector was designed with a loxP-flanked STOP cassette upstream of the open reading frame of the simian Diphtheria Toxin Receptor (DTR; from simian hbEGF cDNA (base pair 56-682)). The loxP-flanked region contains two SV40 polyA signals, an frt-flanked neomycin resistance gene, and a transcriptional STOP cassette. This construct was inserted into the Gt(ROSA)26Sor locus via electroporation of C57BL/6-derived Bruce4 ES embryonic stem (ES) cells. Correctly targeted ES cells were microinjected in CB20 blastocysts. Progeny of the chimeric founder were maintained on a C57BL/6 background. Stock No. 007900 - C57BL/6-Gt(ROSA)26Sor^{tm1(HBEGF)Awai}/J were backcrossed to NOD/ShiLtDvs for 11 generations. In 2011, the Type 1 Diabetes Resource received heterozygous mice at generation N12.

Allele

Symbol: Gt(ROSA)26Sor^{tm1(HBEGF)Awai}
Name: targeted mutation 1, Ari Waisman
MGI accession ID: MGI:3772576
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); Inserted expressed sequence
Marker symbol: Gt(ROSA)26Sor
Marker name: gene trap ROSA 26, Philippe Soriano
Chromosome: 6
Strain of origin: B6.Cg-Thy1^a
Expressed genes: HBEGF,heparin binding EGF like growth factor,chimpanzee; DTR,Simian Diphtheria Toxin Receptor,
Molecular note: A targeting vector was designed with a loxP-flanked STOP cassette upstream of the open reading frame of the simian Diphtheria Toxin Receptor (DTR; from simian hbEGF cDNA (base pair 56-682)). The loxP-flanked region contains two SV40 polyA signals, an frt-flanked neomycin resistance gene, and a transcriptional STOP cassette. This construct was inserted into the Gt(ROSA)26Sor locus via electroporation of C57BL/6-derived Bruce4 ES embryonic stem (ES) cells. Widespread expression of DTR is blocked by an upstream loxP-flanked STOP sequence. When bred to Cre recombinase-expressing mice, the STOP sequence is deleted in tissues where Cre is present, permitting DTR expression. Cells expressing DTR are rendered susceptible to ablation following Diphtheria toxin administration.