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| These mice harbor the "miR-17-92 transgene" targeted to the Gt(ROSA)26Sor locus. The "miR-17-92 transgene" has a loxP-flanked Neo-STOP cassette preventing transcription of the downstream human miR-17-92 cluster (encoding the precursor of seven miRNA molecules; miR-17-5p, miR-17-3p, miR-18a, miR-19a, miR-20a, miR-19b and miR-92). 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 human miR-17-92 cluster. These miR-17-92 transgenic mice allow inducible expression of the human miR-17-92 cluster which has been associated with lymphomas and other cancers, autoimmune defects, and altered expression of tumor suppressor and pro-apoptotic genes. | |||||||||||||||
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Description
Strain Information
Type Coisogenic; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Homozygote x Homozygote (Female x Male) 16-JUL-09 Species laboratory mouse Generation F?+ (02-FEB-09) Donating Investigator Klaus Rajewsky, Immune Disease Institute (formerly CBRI) Description
Mice homozygous for the "miR-17-92 transgene" conditional allele are viable and fertile, with a loxP-flanked Neo-STOP cassette preventing transcription of the downstream bicistronic sequences (human miR-17-92 cluster (encoding the precursor of seven miRNA molecules; miR-17-5p, miR-17-3p, miR-18a, miR-19a, miR-20a, miR-19b and miR-92) 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 human miR-17-92 cluster. Because the synthetic CAG promoter driven miR-17-92 transgene was targeted for insertion into the Gt(ROSA)26Sor locus, expression of the transgene is determined by which tissue(s) express Cre recombinase. EGFP fluorescence, however, is not reported following exposure to Cre recombinase (presumably due to RNaseIII excision of the stem-loop structures encoding individual miRNA destabilizing the EGFP portion of the primary transcript). These miR-17-92 transgenic mice allow inducible expression of the human miR-17-92 cluster that has been associated with lymphomas and other cancers, autoimmune defects, and altered expression of tumor suppressor and pro-apoptotic genes.Development
The "miR-17-92 transgene" was designed with (from 5' to 3') a synthetic CAG promoter, a loxP-flanked Neo-STOP cassette, a genomic DNA fragment encoding the human miR-17-92 cluster (encoding the precursor of seven miRNA molecules; miR-17-5p, miR-17-3p, miR-18a, miR-19a, miR-20a, miR-19b and miR-92), a frt-flanked internal ribosomal entry site-enhanced green fluorescent protein (IRES-EGFP), and polyadenylation signal. This transgene was inserted between exons 1 and 2 of the Gt(ROSA)26Sor locus via electroporation into C57BL/6-derived Bruce-4 embryonic stem (ES) cells. Correctly targeted ES cells were selected and chimeric animals were bred to generate mutant mice. These "miR-17-92 transgenic" mice were maintained on a C57BL/6 genetic background as a homozygous colony for many generations prior to arrival at The Jackson Laboratory. Upon arrival, mice were bred with C57BL/6J inbred mice for at least one generation to establish the colony.
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
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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.Gt(ROSA)26Sortm3(CAG-MIRN17-92,-EGFP)Rsky/Gt(ROSA)26Sor+ Tg(CD2-cre)4Kio/0
involves: C57BL/6 * C57BL/10 * CBA/Ca (conditional)
- immune system phenotype
- decreased marginal zone B cell number (MGI Ref ID J:133215)
- increased B-1a cell number (MGI Ref ID J:133215)
- mice exhibit more CD19+B220loCD5+CD43+CD23- B-1a cells in the spleen and peritoneal cavity compared to in wild-type mice
- hematopoietic system phenotype
- decreased marginal zone B cell number (MGI Ref ID J:133215)
- increased B-1a cell number (MGI Ref ID J:133215)
- mice exhibit more CD19+B220loCD5+CD43+CD23- B-1a cells in the spleen and peritoneal cavity compared to in wild-type mice
Gt(ROSA)26Sortm3(CAG-MIRN17-92,-EGFP)Rsky/Gt(ROSA)26Sortm3(CAG-MIRN17-92,-EGFP)Rsky Tg(CD2-cre)4Kio/0
involves: C57BL/6 * C57BL/10 * CBA/Ca (conditional)
- life span-post-weaning/aging
- premature death (MGI Ref ID J:133215)
- all mice die by 55 weeks of age
- immune system phenotype
- *normal* immune system phenotype (MGI Ref ID J:133215)
- despite increased immunoglobulin, cytokine levels in the blood are normal
- abnormal immune system morphology (MGI Ref ID J:133215)
- abnormal B cell morphology (MGI Ref ID J:133215)
- spleen and lymph node B cells exhibit increased cell size compared to in wild-type mice
- abnormal B cell activation (MGI Ref ID J:133215)
- B cells are more resistance than in wild-type mice to Fas-mediated cell death following activation
- activated B cells exhibit enhanced proliferation and survival compared to wild-type cells
- increased B cell proliferation (MGI Ref ID J:133215)
- B-2 cell proliferation is enhanced following activation with anti-IgM or lipopolysaccharides unlike in wild-type cells
- decreased marginal zone B cell number (MGI Ref ID J:133215)
- increased B cell number (MGI Ref ID J:133215)
- abnormal CD4-positive T cell morphology (MGI Ref ID J:133215)
- CD4+ T cells exhibit increased proliferation and survival following stimulation with CD3 alone unlike wild-type cells
- increased CD4-positive T cell number (MGI Ref ID J:133215)
- abnormal T cell differentiation (MGI Ref ID J:133215)
- prior to 14 weeks of age, mice exhibit a 2-fold higher percentage of thymocytes at the double negative stage compared to in wild-type mice
- however, the total number of thymocytes is unchanged
- abnormal T cell activation (MGI Ref ID J:133215)
- activated T cells exhibit enhanced proliferation and survival compared to wild-type cells
- abnormal spleen marginal zone morphology (MGI Ref ID J:133215)
- the spleen marginal zone is disrupted unlike in wild-type mice
- decreased marginal zone B cell number (MGI Ref ID J:133215)
- decreased spleen red pulp amount (MGI Ref ID J:133215)
- enlarged lymph nodes (MGI Ref ID J:133215)
- spleens and lymph nodes are enlarged up to 30-fold in terms of weight and cell number compared to in wild-type mice
- lymph node hyperplasia (MGI Ref ID J:133215)
- spleens and lymph nodes are enlarged up to 30-fold in terms of weight and cell number compared to in wild-type mice
- increased lymphocyte cell number (MGI Ref ID J:133215)
- at 5 weeks of age
- increased B cell number (MGI Ref ID J:133215)
- increased B-1a cell number (MGI Ref ID J:133215)
- mice exhibit more CD19+B220loCD5+CD43+CD23- B-1a cells in the spleen and peritoneal cavity compared to in wild-type mice
- increased germinal center B cell number (MGI Ref ID J:133215)
- in the spleen and peripheral lymph nodes
- increased CD4-positive T cell number (MGI Ref ID J:133215)
- increased CD8-positive T cell number (MGI Ref ID J:133215)
- increased spleen weight (MGI Ref ID J:133215)
- spleens and lymph nodes are enlarged up to 30-fold in terms of weight and cell number compared to in wild-type mice
- increased spleen white pulp amount (MGI Ref ID J:133215)
- intermingled spleen red and white pulp (MGI Ref ID J:133215)
- spleen hyperplasia (MGI Ref ID J:133215)
- spleens and lymph nodes are enlarged up to 30-fold in terms of weight and cell number compared to in wild-type mice
- abnormal immune system physiology (MGI Ref ID J:133215)
- mice exhibit massive infiltration of lymphocytes into the salivary glands and lungs with some infiltration of the kidneys unlike in wild-type mice
- abnormal CD4-positive T cell physiology (MGI Ref ID J:133215)
- more CD4+ T cells produce IFN-gamma and IL-10 but not IL-4 or TNF than wild-type cells
- CD4+T cells from older mice produce more IFN-gamma and IL-10 than CD4+ T cells from younger mice
- abnormal immunoglobulin level (MGI Ref ID J:133215)
- increased IgG2a level (MGI Ref ID J:133215)
- 4- to 6-fold at 8 to 12 weeks of age
- increased IgG2b level (MGI Ref ID J:133215)
- 4- to 6-fold at 8 to 12 weeks of age
- increased IgG3 level (MGI Ref ID J:133215)
- 4- to 6-fold at 8 to 12 weeks of age
- increased IgM level (MGI Ref ID J:133215)
- 4- to 6-fold at 8 to 12 weeks of age
- increased anti-double stranded DNA antibody level (MGI Ref ID J:133215)
- at 18 to 25 weeks
- increased anti-single stranded DNA antibody level (MGI Ref ID J:133215)
- at 18 to 25 weeks
- renal/urinary system phenotype
- abnormal renal glomerulus morphology (MGI Ref ID J:133215)
- mice exhibit enlarged renal glomeruli with hypercellularity and mesangial expansion unlike in wild-type mice
- abnormal mesangial cell (MGI Ref ID J:133215)
- mice exhibit mesangial expansion unlike in wild-type mice
- pale kidney (MGI Ref ID J:133215)
- in some mice
- proteinuria (MGI Ref ID J:133215)
- in some mice
- homeostasis/metabolism phenotype
- proteinuria (MGI Ref ID J:133215)
- in some mice
- hematopoietic system phenotype
- abnormal B cell morphology (MGI Ref ID J:133215)
- spleen and lymph node B cells exhibit increased cell size compared to in wild-type mice
- abnormal B cell activation (MGI Ref ID J:133215)
- B cells are more resistance than in wild-type mice to Fas-mediated cell death following activation
- activated B cells exhibit enhanced proliferation and survival compared to wild-type cells
- increased B cell proliferation (MGI Ref ID J:133215)
- B-2 cell proliferation is enhanced following activation with anti-IgM or lipopolysaccharides unlike in wild-type cells
- decreased marginal zone B cell number (MGI Ref ID J:133215)
- increased B cell number (MGI Ref ID J:133215)
- abnormal CD4-positive T cell morphology (MGI Ref ID J:133215)
- CD4+ T cells exhibit increased proliferation and survival following stimulation with CD3 alone unlike wild-type cells
- increased CD4-positive T cell number (MGI Ref ID J:133215)
- abnormal T cell differentiation (MGI Ref ID J:133215)
- prior to 14 weeks of age, mice exhibit a 2-fold higher percentage of thymocytes at the double negative stage compared to in wild-type mice
- however, the total number of thymocytes is unchanged
- abnormal T cell activation (MGI Ref ID J:133215)
- activated T cells exhibit enhanced proliferation and survival compared to wild-type cells
- abnormal spleen marginal zone morphology (MGI Ref ID J:133215)
- the spleen marginal zone is disrupted unlike in wild-type mice
- decreased marginal zone B cell number (MGI Ref ID J:133215)
- decreased spleen red pulp amount (MGI Ref ID J:133215)
- extramedullary hematopoiesis (MGI Ref ID J:133215)
- increased lymphocyte cell number (MGI Ref ID J:133215)
- at 5 weeks of age
- increased B cell number (MGI Ref ID J:133215)
- increased B-1a cell number (MGI Ref ID J:133215)
- mice exhibit more CD19+B220loCD5+CD43+CD23- B-1a cells in the spleen and peritoneal cavity compared to in wild-type mice
- increased germinal center B cell number (MGI Ref ID J:133215)
- in the spleen and peripheral lymph nodes
- increased CD4-positive T cell number (MGI Ref ID J:133215)
- increased CD8-positive T cell number (MGI Ref ID J:133215)
- increased spleen weight (MGI Ref ID J:133215)
- spleens and lymph nodes are enlarged up to 30-fold in terms of weight and cell number compared to in wild-type mice
- increased spleen white pulp amount (MGI Ref ID J:133215)
- intermingled spleen red and white pulp (MGI Ref ID J:133215)
- spleen hyperplasia (MGI Ref ID J:133215)
- spleens and lymph nodes are enlarged up to 30-fold in terms of weight and cell number compared to in wild-type mice
This mouse can be used to support research in many areas including:
Apoptosis Research
Endogenous Regulators
Autoimmune Lymphroliferatve syndrome
Cancer Research
Increased Tumor Incidence
Lymphomas
Tumor Suppressor Genes
Developmental Biology Research
Internal/Organ Defects
Lymphoid Tissue Defects
Lymphoid Tissue Defects
Immunology and Inflammation Research
Autoimmunity
Lymphoid Tissue Defects
Internal/Organ Research
Lymphoid Tissue Defects
Mouse/Human Gene Homologs
autoimmune lymphoproliferative syndrome
Research Tools
Apoptosis Research
Cancer Research
genes regulating lymphoma development
Cre-lox System
loxP-flanked Sequences
Developmental Biology Research
Cre-lox System
Fluorescent Proteins
Genetics Research
Mutagenesis and Transgenesis: Cre-lox System
Tissue/Cell Markers: Cre-lox System
Immunology and Inflammation Research
B cell lymphomas
Internal/Organ Research
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Gt(ROSA)26Sortm3(CAG-MIRN17-92,-EGFP)Rsky | ||
|---|---|---|---|
| Allele Name | targeted mutation 3, Klaus Rajewsky | ||
| Allele Type | Targeted (Reporter) | ||
| Common Name(s) | Gt(ROSA)26Sortm3Rsky; | ||
| 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 | ||
| 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 | A cassette containing the chicken beta actin promoter CAG driving the expression of a floxed neo-STOP cassette followed by cDNA encoding human MIRN 17, 18a, 19a, 20a, 19b and 92 plus an frt-flanked IRES-EGFP cassette and a poly-adenylation site were inserted into the ROSA locus. This allele is also a knockin allele that allows for expression of the human MIRNs contained within it following the cre-mediated removal of the neo-STOP cassette. [MGI Ref ID J:133215] | ||
Genotyping
Genotyping Information
This strain will not have a genotyping protocol or one is not currently available.
Helpful Links
Genotyping resources and troubleshooting
References
References
Selected Reference(s)
Xiao C; Srinivasan L; Calado DP; Patterson HC; Zhang B; Wang J; Henderson JM; Kutok JL; Rajewsky K. 2008. Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes. Nat Immunol 9(4):405-14. [PubMed: 18327259] [MGI Ref ID J:133215]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number MGL375/MGL377
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, homozygous mice may be bred together. Mating System Homozygote x Homozygote (Female x Male) 16-JUL-09
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)26Sortm3(CAG-MIRN17-92,-EGFP)Rsky
Pairs /Price (US dollars $) Pair Genotype $320.80 Homozygous for Gt(ROSA)26Sortm3(CAG-MIRN17-92,-EGFP)Rsky x Homozygous for Gt(ROSA)26Sortm3(CAG-MIRN17-92,-EGFP)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)26Sortm3(CAG-MIRN17-92,-EGFP)Rsky
Pairs /Price (US dollars $) Pair Genotype $417.10 Homozygous for Gt(ROSA)26Sortm3(CAG-MIRN17-92,-EGFP)Rsky x Homozygous for Gt(ROSA)26Sortm3(CAG-MIRN17-92,-EGFP)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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