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| These R26StopFLikk2ca mice allow inducible expression of an activated form of Ikbkb (IKK2ca) and subsequent activation of the NF-kappaB transcription factor pathways. | |||||||||||||||
- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
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Description
Strain Information
Former Names C57BL/6-Gt(ROSA)26Sortm1(Ikbkb)Mass/J (Changed: 12-AUG-08 ) Type Coisogenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Homozygote x Homozygote (Female x Male) 03-DEC-08 Species laboratory mouse Generation F?+N1F3 (18-AUG-09) Donating Investigator Klaus Rajewsky, Immune Disease Institute (formerly CBRI) Description
Mice homozygous for the R26StopFLikk2ca conditional allele are viable and fertile, with a loxP-flanked STOP cassette preventing transcription of the downstream bicistronic sequences (a FLAG-tagged, constitutively active form of IKbkb (IKK2ca) and EGFP). When bred to mice that express Cre recombinase, the resulting offspring will have the STOP cassette deleted in the cre-expressing tissue(s); resulting in expression of the IKK2ca as well as EGFP fluorescence. Expression of IKK2ca leads to constitutively active NF-kappaB transcription factor activity. These R26StopFLikk2ca mice allow inducible expression of an activated form of Ikbkb (IKK2 or IKK-beta) and subsequent activation of the NF-kappaB transcription factor pathways.For example, when bred to a strain with a Cd19 null allele and expressing Cre recombinase during the B lymphocyte development (Stock No. 006785), this mutant mouse strain may be useful in studies of the NF-kappaB pathway.
Development
A 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 IKbkb (IKK2ca; containing two serine to glutamate substitutions (S177E, S181E) in the activation loop of the kinase 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 and chimeric animals were bred to C57BL/6 mice to generate mutant mice. These R26StopFLikk2ca mice were maintained as a homozygous colony for many generations prior to arrival at The Jackson Laboratory.
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
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Additional Web Information
FLP-FRT Systems
Fluorescent Proteins/lacZ Systems
Introduction to Cre-lox technology
Phenotype
Phenotype Information
assigned by genotype
The following phenotype relates to a compound genotype created using this strain.
Contact JAX® Services jaxservices@jax.org for customized breeding options.Cd19tm1(cre)Cgn/Cd19+ Gt(ROSA)26Sortm4(Ikbkb)Rsky/Gt(ROSA)26Sor+
involves: 129P2/OlaHsd * C57BL/6 (conditional)
- cellular phenotype
- increased cell proliferation (MGI Ref ID J:113365)
- 1-2 days after crosslinking with BCR, there are more cells is S phase than in wild-type B cell cultures
- immune system phenotype
- abnormal B cell physiology (MGI Ref ID J:113365)
- cells on average have a longer lifespan than wild-type B cells
- decreased B cell apoptosis (MGI Ref ID J:113365)
- 1-2 days after crosslinking with BCR, there are less apoptotic cells than in purified wild-type B cell cultures
- abnormal splenic cell ratio (MGI Ref ID J:113365)
- B cell hyperplasia is observed, with a significantly expanded population of marginal zone B cells
- increased B cell number (MGI Ref ID J:113365)
- B cell numbers are increased in spleens (130 x 106) compared to wild-type (56 x 106)
- hematopoietic system phenotype
- abnormal splenic cell ratio (MGI Ref ID J:113365)
- B cell hyperplasia is observed, with a significantly expanded population of marginal zone B cells
- increased B cell number (MGI Ref ID J:113365)
- B cell numbers are increased in spleens (130 x 106) compared to wild-type (56 x 106)
This mouse can be used to support research in many areas including:
Cancer Research
Growth Factors/Receptors/Cytokines
Cell Biology Research
Signal Transduction
Transcriptional Regulation
Immunology and Inflammation Research
Growth Factors/Receptors/Cytokines
Intracellular Signaling Molecules
Neurobiology Research
Cre-lox System
loxP-flanked Sequences
Fluorescent protein expression in neural tissue
Research Tools
Cancer Research
Cell Biology Research
Cre-lox System
loxP-flanked Sequences
FLP-FRT System
FRT-flanked Sequences
Fluorescent Proteins
Genetics Research
Mutagenesis and Transgenesis: transcriptional activation
Tissue/Cell Markers: Cre-lox System
Tissue/Cell Markers: multiple
Immunology and Inflammation Research
Neurobiology Research
cell marker
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Gt(ROSA)26Sortm4(Ikbkb)Rsky | ||
|---|---|---|---|
| Allele Name | targeted mutation 4, Klaus Rajewsky | ||
| Allele Type | Targeted (knock-in) | ||
| Common Name(s) | Gt(ROSA)26Sortm1(Ikbkb)Mass; R26StopFLikk2ca; | ||
| Mutation Made By | Klaus Rajewsky, Immune Disease Institute (formerly CBRI) | ||
| Strain of Origin | C57BL/6 | ||
| ES Cell Line Name | Bruce 4 | ||
| ES Cell Line Strain | C57BL/6 | ||
| Site of Expression | Expression of the bicistronic sequences (a constitutively active form of IKbkb (IKK2ca) and EGFP) is blocked by a loxP-flanked STOP cassette. When bred to Cre recombinase expressing mice, the loxP-flanked STOP cassette is removed, resulting in expression of the IKK2ca and EGFP in Cre recombinase expressing cells. | ||
| Gene Symbol and Name | Gt(ROSA)26Sor, gene trap ROSA 26, Philippe Soriano | ||
| Chromosome | 6 | ||
| Gene Common Name(s) | AV258896; Gtrgeo26; Gtrosa26; R26; ROSA26; beta geo; expressed sequence AV258896; gene trap ROSA 26; gene trap ROSA b-geo 26; | ||
| Molecular Note | An IRES-eGFP cassette and a cDNA sequence encoding Ikbkb containing two serine to glutamate substitutions in the activation loop of the kinase domain, preceded by a floxed stop-neo cassette was inserted into the locus. The Ikbkb would be expressed under the control of the endogenous ROSA26 promoter after cre-mediated excision of the STOP cassette. [MGI Ref ID J:113365] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Gt(ROSA)26Sortm1(Ikbkb)Mass, Separated PCR
Helpful Links
Genotyping resources and troubleshooting
References
References
Selected Reference(s)
Sasaki Y; Derudder E; Hobeika E; Pelanda R; Reth M; Rajewsky K; Schmidt-Supprian M. 2006. Canonical NF-kappaB activity, dispensable for B cell development, replaces BAFF-receptor signals and promotes B cell proliferation upon activation. Immunity 24(6):729-39. [PubMed: 16782029] [MGI Ref ID J:113365]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, homozygous mice may be bred. Mating System Homozygote x Homozygote (Female x Male) 03-DEC-08 Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $160.40 Female or Male Homozygous for Gt(ROSA)26Sortm1(Ikbkb)Rsky
Pairs /Price (US dollars $) Pair Genotype $320.80 Homozygous for Gt(ROSA)26Sortm1(Ikbkb)Rsky x Homozygous for Gt(ROSA)26Sortm1(Ikbkb)Rsky
Additional Supply Details
| Pricing for International shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $208.60 Female or Male Homozygous for Gt(ROSA)26Sortm1(Ikbkb)Rsky
Pairs /Price (US dollars $) Pair Genotype $417.10 Homozygous for Gt(ROSA)26Sortm1(Ikbkb)Rsky x Homozygous for Gt(ROSA)26Sortm1(Ikbkb)Rsky
Additional Supply Details
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Supply Details
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of approximately nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within two business days following order placement. |
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| Supply Notes |
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Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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