Mice homozygous for the NIK-deltaT3 allele are viable and fertile, with a loxP-flanked Neo-STOP cassette preventing transcription of the downstream bicistronic sequences (NIKdeltaT3 [a constitutively active form of the mouse NF-kappaB inducing kinase] and EGFP).
Klaus Rajewsky, Max Delbruck Centre for Molecular Medicine
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Conditional ready (e.g. floxed), Reporter, Inserted expressed sequence) | Gt(ROSA)26Sor | gene trap ROSA 26, Philippe Soriano |
Mice homozygous for the NIK-deltaT3 allele are viable and fertile, with a loxP-flanked Neo-STOP cassette preventing transcription of the downstream bicistronic sequences (NIKdeltaT3 [a constitutively active form of the mouse NF-kappaB inducing kinase] and EGFP). When bred to mice that express Cre recombinase, offspring will have the STOP cassette deleted and subsequent expression of the NIKdeltaT3 molecule and EGFP fluorescence in the cre-expressing cells. Expression of NIK-deltaT3 leads to uncoupling NIK from tumor necrosis factor receptor-associated factor 3 (TRAF3)-mediated control causing maximal p100 processing and dramatic hyperplasia of B cell-activating factor
of the TNF family receptor (BAFF-R)-independent B cells. BAFF-R binding is required to sustain the NIK p100 subunit processing needed for B cell survival, as implicated in human multiple myeloma.
Of note, breeding these mice to an FLP-expressing strain will result in removal of the frt-flanked IRES-EGFP cassette.
When bred to a strain expressing Cre recombinase throughout B lymphocyte development and differentiation (see Stock No. 006785 for example), this mutant mouse strain exhibits increased B cell numbers.
The NIK-deltaT3 targeting vector was designed with (from 5' to 3') a loxP-flanked neomycin resistance-STOP cassette, a cDNA encoding a FLAG-tagged, constitutively active form of murine NF-kappaB inducing kinase (NIKdeltaT3, NIK mutant lacking the Traf3 binding domain), a frt-flanked internal ribosomal entry site and enhanced green fluorescent protein (IRES-EGFP), and a bovine polyA sequence. This construct was placed under control of the promoter of the targeted gene via electroporation into C57BL/6-derived Bruce-4 embryonic stem (ES) cells. Correctly targeted ES cells were selected, injected into blastocysts and chimeric animals were bred to C57BL/6 mice to generate mutant mice. These R26-STOP-NIKdelta3 mice were maintained as a homozygous colony for many generations. Upon arrival at The Jackson Laboratory, mutant mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.
Expressed Gene | GFP, Green Fluorescent Protein, |
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Expressed Gene | Map3k14, mitogen-activated protein kinase kinase kinase 14, mouse, laboratory |
Site of Expression | When bred to mice that express Cre recombinase, bicistronic expression of GFP and NIKdeltaT3 (a constitutively active form of the mouse NF-kappaB inducing kinase, Map3k14) will occur in cells where promoters driving Cre recombinase are expressed. |
Allele Name | targeted mutation 6, Klaus Rajewsky |
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Allele Type | Targeted (Conditional ready (e.g. floxed), Reporter, Inserted expressed sequence) |
Allele Synonym(s) | R26StopFLNikdeltaT3 |
Gene Symbol and Name | Gt(ROSA)26Sor, gene trap ROSA 26, Philippe Soriano |
Gene Synonym(s) | |
Expressed Gene | GFP, Green Fluorescent Protein, |
Expressed Gene | Map3k14, mitogen-activated protein kinase kinase kinase 14, mouse, laboratory |
Site of Expression | When bred to mice that express Cre recombinase, bicistronic expression of GFP and NIKdeltaT3 (a constitutively active form of the mouse NF-kappaB inducing kinase, Map3k14) will occur in cells where promoters driving Cre recombinase are expressed. |
Strain of Origin | B6.Cg-Thy1a |
Chromosome | 6 |
Molecular Note | The gene lacking the sequence that encodes the TRAF3-binding domain, preceded by a floxed neo STOP cassette and followed by an frt-flanked IRES-EGFP cassette, was knocked into the locus to achieve cre-inducible, ubiquitous expression. Cre mediated removal of the STOP cassette is required for expression. |
Mutations Made By | Klaus Rajewsky, Max Delbruck Centre for Molecular Medicine |
When maintaining a live colony, homozygous mice may be bred together.
When using the C57BL/6-Gt(ROSA)26Sortm6(Map3k14*)Rsky/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #012638 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous for Gt(ROSA)26Sor<tm6(Map3k14*)Rsky> |
Frozen Mouse Embryo | C57BL/6-Gt(ROSA)26Sor<tm6(Map3k14*)Rsky>/J | $2595.00 |
Frozen Mouse Embryo | C57BL/6-Gt(ROSA)26Sor<tm6(Map3k14*)Rsky>/J | $2595.00 |
Frozen Mouse Embryo | C57BL/6-Gt(ROSA)26Sor<tm6(Map3k14*)Rsky>/J | $3373.50 |
Frozen Mouse Embryo | C57BL/6-Gt(ROSA)26Sor<tm6(Map3k14*)Rsky>/J | $3373.50 |
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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