Overview

Also Known As: miR-17-92

These mice harbor the miR-17-92 transgene targeted to the Gt(ROSA)26Sor locus. miR-17-92 transgenic mice allow the cre-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.

Donating Investigator

Klaus Rajewsky, Max Delbruck Centre for Molecular Medicine

Genetic overview

Genetic Background	Generation

Gt(ROSA)26Sor^{tm3(CAG-MIR17-92,-EGFP)Rsky}

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), Reporter, Humanized sequence, No functional change)	Gt(ROSA)26Sor	gene trap ROSA 26, Philippe Soriano

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Research Applications

Research Tools
Apoptosis Research
Developmental Biology Research
Mouse/Human Gene Homologs
Cancer Research
Immunology, Inflammation and Autoimmunity Research
Internal/Organ Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed 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 (see SNP note below). Upon arrival at The Jackson Laboratory, mice were bred with C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 2 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.

Expression Data

Expressed Gene	GFP, Green Fluorescent Protein,
Expressed Gene	Mirn17-92, microRNA cluster 17-92,
Site of Expression	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. EGFP fluorescence, however, is not reported following exposure to Cre recombinase.

Control Suggestions

Approximate Controls

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

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):405-14PubMed: 18327259 MGI: J:133215

View All References

Genetics

Gt(ROSA)26Sor^{tm3(CAG-MIR17-92,-EGFP)Rsky}

Allele Symbol: Gt(ROSA)26Sor^{tm3(CAG-MIR17-92,-EGFP)Rsky}

Allele Name	targeted mutation 3, Klaus Rajewsky
Allele Type	Targeted (Conditional ready (e.g. floxed), Reporter, Humanized sequence, No functional change)
Allele Synonym(s)	targeted mutation 3, Klaus Rajewsky; Gt(ROSA)26Sor^{tm3(CAG-MIR17-92,-EGFP)Rsky}
Gene Symbol and Name	Gt(ROSA)26Sor, gene trap ROSA 26, Philippe Soriano
Gene Synonym(s)	beta geo; ROSA26; R26; Gtrgeo26; Gtrosa26; Gtrgeo26; Gtrosa26; AV258896; expressed sequence AV258896; gene trap ROSA 26; gene trap ROSA b-geo 26; SETD5-AS1; Thumpd3as1
Promoter	CAG, CMV-IE enhancer/chicken beta-actin/rabbit beta-globin hybrid promoter,
Expressed Gene	GFP, Green Fluorescent Protein,
Expressed Gene	Mirn17-92, microRNA cluster 17-92,
Site of Expression	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. EGFP fluorescence, however, is not reported following exposure to Cre recombinase.
Strain of Origin	B6.Cg-Thy1^a
Chromosome	6
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.
Mutations Made By	Klaus Rajewsky, Max Delbruck Centre for Molecular Medicine

Disease/Phenotype

Disease Terms

Research Areas By Genotype

This mouse can be used to support research in many areas including:

Research Tools
- Genetics Research
  - Tissue/Cell Markers
  - Tissue/Cell Markers: Cre-lox System
  - Mutagenesis and Transgenesis
  - Mutagenesis and Transgenesis: Cre-lox System
- Developmental Biology Research
  - Cre-lox System
- Cre-lox System
  - loxP-flanked Sequences
- Apoptosis Research
- Internal/Organ Research
- Cancer Research
  - genes regulating lymphoma development
- Immunology, Inflammation and Autoimmunity Research
  - B cell lymphomas
Apoptosis Research
- Endogenous Regulators
  - Autoimmune Lymphroliferatve syndrome
Developmental Biology Research
- Lymphoid Tissue Defects
- Internal/Organ Defects
  - Lymphoid Tissue Defects
Mouse/Human Gene Homologs
- autoimmune lymphoproliferative syndrome
Cancer Research
- Tumor Suppressor Genes
- Increased Tumor Incidence
  - Lymphomas
Immunology, Inflammation and Autoimmunity Research
- Autoimmunity
- Lymphoid Tissue Defects
Internal/Organ Research
- Lymphoid Tissue Defects

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Gt(ROSA)26Sor^{tm3(CAG-MIR17-92,-EGFP)Rsky}/Gt(ROSA)26Sor⁺ Tg(CD2-icre)4Kio/0
involves: C57BL/6 * C57BL/10 * CBA/Ca

hematopoietic system phenotype

decreased marginal zone B cell number

increased B-1a cell number
- mice exhibit more CD19+B220^loCD5+CD43+CD23- B-1a cells in the spleen and peritoneal cavity compared to in wild-type mice

immune system phenotype

decreased marginal zone B cell number

increased B-1a cell number
- mice exhibit more CD19+B220^loCD5+CD43+CD23- B-1a cells in the spleen and peritoneal cavity compared to in wild-type mice

Genotype: Gt(ROSA)26Sor^{tm3(CAG-MIR17-92,-EGFP)Rsky}/Gt(ROSA)26Sor^{tm3(CAG-MIR17-92,-EGFP)Rsky} Tg(CD2-icre)4Kio/0
involves: C57BL/6 * C57BL/10 * CBA/Ca

cellular phenotype

increased B cell proliferation
- B-2 cell proliferation is enhanced following activation with anti-IgM or lipopolysaccharides unlike in wild-type cells

hematopoietic system phenotype

abnormal B cell activation
- activated B cells exhibit enhanced proliferation and survival compared to wild-type cells
- B cells are more resistance than in wild-type mice to Fas-mediated cell death following activation

abnormal B cell morphology
- spleen and lymph node B cells exhibit increased cell size compared to in wild-type mice

abnormal CD4-positive, alpha beta T cell morphology
- CD4+ T cells exhibit increased proliferation and survival following stimulation with CD3 alone unlike wild-type cells

abnormal CD4-positive, alpha-beta T cell physiology
- CD4+T cells from older mice produce more IFN-gamma and IL-10 than CD4+ T cells from younger mice
- more CD4+ T cells produce IFN-gamma and IL-10 but not IL-4 or TNF than wild-type cells

abnormal immunoglobulin level

abnormal spleen marginal zone morphology
- the spleen marginal zone is disrupted unlike in wild-type mice

abnormal T cell activation
- activated T cells exhibit enhanced proliferation and survival compared to wild-type cells

abnormal T cell differentiation
- Normal - however, the total number of thymocytes is unchanged
- 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

decreased marginal zone B cell number

decreased spleen red pulp amount

extramedullary hematopoiesis

increased B cell number

increased B cell proliferation
- B-2 cell proliferation is enhanced following activation with anti-IgM or lipopolysaccharides unlike in wild-type cells

increased B-1a cell number
- mice exhibit more CD19+B220^loCD5+CD43+CD23- B-1a cells in the spleen and peritoneal cavity compared to in wild-type mice

increased CD4-positive, alpha beta T cell number

increased CD8-positive, alpha-beta T cell number

increased germinal center B cell number
- in the spleen and peripheral lymph nodes

increased IgG2a level
- 4- to 6-fold at 8 to 12 weeks of age

increased IgG2b level
- 4- to 6-fold at 8 to 12 weeks of age

increased IgG3 level
- 4- to 6-fold at 8 to 12 weeks of age

increased IgM level
- 4- to 6-fold at 8 to 12 weeks of age

increased lymphocyte cell number
- at 5 weeks of age

increased spleen weight
- 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

intermingled spleen red and white pulp

spleen hyperplasia
- spleens and lymph nodes are enlarged up to 30-fold in terms of weight and cell number compared to in wild-type mice

homeostasis/metabolism phenotype

increased urine protein level
- in some mice

immune system phenotype

abnormal B cell activation
- activated B cells exhibit enhanced proliferation and survival compared to wild-type cells
- B cells are more resistance than in wild-type mice to Fas-mediated cell death following activation

abnormal B cell morphology
- spleen and lymph node B cells exhibit increased cell size compared to in wild-type mice

abnormal CD4-positive, alpha beta T cell morphology
- CD4+ T cells exhibit increased proliferation and survival following stimulation with CD3 alone unlike wild-type cells

abnormal CD4-positive, alpha-beta T cell physiology
- CD4+T cells from older mice produce more IFN-gamma and IL-10 than CD4+ T cells from younger mice
- more CD4+ T cells produce IFN-gamma and IL-10 but not IL-4 or TNF than wild-type cells

abnormal immune system morphology

abnormal immune system physiology
- mice exhibit massive infiltration of lymphocytes into the salivary glands and lungs with some infiltration of the kidneys unlike in wild-type mice

abnormal immunoglobulin level

abnormal spleen marginal zone morphology
- the spleen marginal zone is disrupted unlike in wild-type mice

abnormal T cell activation
- activated T cells exhibit enhanced proliferation and survival compared to wild-type cells

abnormal T cell differentiation
- Normal - however, the total number of thymocytes is unchanged
- 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

decreased marginal zone B cell number

decreased spleen red pulp amount

enlarged lymph nodes
- spleens and lymph nodes are enlarged up to 30-fold in terms of weight and cell number compared to in wild-type mice

increased anti-double stranded DNA antibody level
- at 18 to 25 weeks

increased anti-single stranded DNA antibody level
- at 18 to 25 weeks

increased B cell number

increased B cell proliferation
- B-2 cell proliferation is enhanced following activation with anti-IgM or lipopolysaccharides unlike in wild-type cells

increased B-1a cell number
- mice exhibit more CD19+B220^loCD5+CD43+CD23- B-1a cells in the spleen and peritoneal cavity compared to in wild-type mice

increased CD4-positive, alpha beta T cell number

increased CD8-positive, alpha-beta T cell number

increased germinal center B cell number
- in the spleen and peripheral lymph nodes

increased IgG2a level
- 4- to 6-fold at 8 to 12 weeks of age

increased IgG2b level
- 4- to 6-fold at 8 to 12 weeks of age

increased IgG3 level
- 4- to 6-fold at 8 to 12 weeks of age

increased IgM level
- 4- to 6-fold at 8 to 12 weeks of age

increased lymphocyte cell number
- at 5 weeks of age

increased spleen weight
- 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

intermingled spleen red and white pulp

lymph node hyperplasia
- spleens and lymph nodes are enlarged up to 30-fold in terms of weight and cell number compared to in wild-type mice

spleen hyperplasia
- spleens and lymph nodes are enlarged up to 30-fold in terms of weight and cell number compared to in wild-type mice

mammalian phenotype

immune system phenotype
- Normal - despite increased immunoglobulin, cytokine levels in the blood are normal

mortality/aging

premature death
- all mice die by 55 weeks of age

renal/urinary system phenotype

abnormal glomerular mesangium morphology
- a subset of mice show marked accumulation of IgG and the C3d component of complement in the mesangium and segmentally in the periphery of glomeruli

expanded mesangial matrix
- mice exhibit mesangial expansion unlike in wild-type mice

increased urine protein level
- in some mice

mesangial cell hyperplasia

pale kidney
- in some mice

renal glomerulus hypertrophy
- mice exhibit enlarged renal glomeruli with hypercellularity and mesangial expansion unlike in wild-type mice

References

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):405-14PubMed: 18327259 MGI: J:133215

Additional - Gt(ROSA)26Sor^{tm3(CAG-MIR17-92,-EGFP)Rsky} related

Technical Support

Contact Technical Support

Genotyping Protocols
- Standard PCR:Gt(ROSA)26Sor^{tm3(CAG-MIR17-92,-EGFP)Rsky}
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, homozygous mice may be bred together.
- Additional Breeding and Husbandry Support
Citation
When using the miR-17-92 mouse strain in a publication, please cite the originating article(s) and include JAX stock #008517 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Heterozygous for Gt(ROSA)26Sor<tm3(CAG-MIRN17-92,-EGFP)Rsky>

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.

Related Products and Services

Frozen Mouse Embryo	C57BL/6-Gt(ROSA)26Sor<tm3(CAG-MIR17-92,-EGFP) Frozen Embryos	$2595.00
Frozen Mouse Embryo	C57BL/6-Gt(ROSA)26Sor<tm3(CAG-MIR17-92,-EGFP) Frozen Embryos	$2595.00
Frozen Mouse Embryo	C57BL/6-Gt(ROSA)26Sor<tm3(CAG-MIR17-92,-EGFP) Frozen Embryos	$3373.50
Frozen Mouse Embryo	C57BL/6-Gt(ROSA)26Sor<tm3(CAG-MIR17-92,-EGFP) Frozen Embryos	$3373.50

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Also Known As: miR-17-92

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Approximate Controls

Additional Information

Selected References

Gt(ROSA)26Sortm3(CAG-MIR17-92,-EGFP)Rsky

Allele Symbol: Gt(ROSA)26Sortm3(CAG-MIR17-92,-EGFP)Rsky

Disease Terms

Research Areas By Genotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

Genotype: Gt(ROSA)26Sortm3(CAG-MIR17-92,-EGFP)Rsky/Gt(ROSA)26Sor+ Tg(CD2-icre)4Kio/0involves: C57BL/6 * C57BL/10 * CBA/Ca

hematopoietic system phenotype

immune system phenotype

Genotype: Gt(ROSA)26Sortm3(CAG-MIR17-92,-EGFP)Rsky/Gt(ROSA)26Sortm3(CAG-MIR17-92,-EGFP)Rsky Tg(CD2-icre)4Kio/0involves: C57BL/6 * C57BL/10 * CBA/Ca

cellular phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

mammalian phenotype

mortality/aging

renal/urinary system phenotype

References

Additional - Gt(ROSA)26Sortm3(CAG-MIR17-92,-EGFP)Rsky related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Gt(ROSA)26Sor^{tm3(CAG-MIR17-92,-EGFP)Rsky}

Allele Symbol: Gt(ROSA)26Sor^{tm3(CAG-MIR17-92,-EGFP)Rsky}

Genotype: Gt(ROSA)26Sor^{tm3(CAG-MIR17-92,-EGFP)Rsky}/Gt(ROSA)26Sor⁺ Tg(CD2-icre)4Kio/0
involves: C57BL/6 * C57BL/10 * CBA/Ca

Genotype: Gt(ROSA)26Sor^{tm3(CAG-MIR17-92,-EGFP)Rsky}/Gt(ROSA)26Sor^{tm3(CAG-MIR17-92,-EGFP)Rsky} Tg(CD2-icre)4Kio/0
involves: C57BL/6 * C57BL/10 * CBA/Ca

Additional - Gt(ROSA)26Sor^{tm3(CAG-MIR17-92,-EGFP)Rsky} related