Overview

Also Known As:Jak2^VF

Jak2^+/VF mice have an inverted exon 14, carrying a valine to phenylalanine mutation (V617F), downstream of the endogenous exon 14 of the Janus kinase 2 (Jak2) gene. Both exons are surrounded by loxP and loxP511 sites, allowing for Cre-mediated removal of the endogenous exon 14 and inversion of the mutated exon 14. These mice may be useful when studying myeloproliferative neoplasm (MPN).

Donating Investigator

Ann Mullally, Brigham and Women's Hospital--Harvard Medical School

Genetic overview

Genetic Background	Generation
	N10+pN1 (2019-03-15 00:00:00)

Jak2^tm1.2Ble

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed))	Jak2	Janus kinase 2

View Genetics

Research Applications

Immunology, Inflammation and Autoimmunity Research
Cell Biology Research
Research Tools

View All Research Applications

Base Price

Starting at:

$255.00 Domestic price for female 4-week

333.51 Domestic price for breeder pair

View Price List

Details

Detailed Description

Jak2^+/VF mice have an inverted exon 14, carrying a valine to phenylalanine mutation (V617F), downstream of the endogenous exon 14 of the Janus kinase 2 (Jak2) gene. Both exons are surrounded by loxP and loxP511 sites, allowing for Cre-mediated removal of the endogenous exon 14 and inversion of the mutated exon 14. The V617F mutation is commonly found in patients with myeloproliferative neoplasm (MPN) and is present in approximately 95% of patients with polycythemia vera (PV) and in approximately 50% of patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF).

JAK2 is a protein tyrosine kinase involved in a specific subset of cytokine receptor signaling pathways and is misregulated or mutated in some myeloproliferative diseases and cancers. The V617F mutation results in constitutive activation of JAK2 kinase signaling. When activated, JAK2 phosphorylates STAT transcription factors and initiates the JAK-STAT signaling pathway. This is the most prevalent JAK2 mutation.

Mice that are heterozygous for this allele are viable and fertile, while floxed homozygous mice are not viable. Lethality may be the result of the targeting construct creating a null allele prior to cre excision. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have the floxed endogenous exon 14 removed and the V617F mutant exon 14 placed into transcriptional orientation.

When mice are bred to a germline or a hematopoietic-specific Cre Recombinase expressing strain such as B6.FVB-Tg(EIIa-cre)C5379Lmgd/J (Stock No. 003724), B6.Cg-Tg(Mx1-cre)1Cgn/J (Stock No. 003556), or VavCre, mice are a model of MPN characterized by elevated hematocrit (HCT), splenomegaly, and prominent splenic extramedullary erythropoiesis. Mice have median survival time of 146 days. They develop lethal 100% penetrant myeloproliferative neoplasms but not acute leukemia. The bone marrow myeloid progenitor compartment is skewed toward the erythroid lineage, which cannot transfer disease. The long-term HSC compartment (CD150+ CD48+ LSK) can transplant the disease into lethally irradiated wild-type recipient mice. When mice are treated with Interferon-α, Jak2^VF MPN-propagating cells are depleted, and the disease cannot be transferred.

Of note crossing primary floxed mice to MxCre results in spontaneous recombination in the absence of pIpC.

Development

The Jak2^VF targeting vector was designed to insert an inverted mutated exon 14 downstream of endogenous exon 14 of the Janus kinase 2 (Jak2) gene. Specifically, the vector included, from 5’ to 3', a loxP site, endogenous exon 14, a loxP511 site, an inverted exon 14, a second loxP site and a second loxP511 site. The inverted exon 14 was modified to harbor a guanine to thymine substitution (G1849T) at amino acid 617, resulting in a valine to phenylalanine mutation (V617F), commonly found in patients with myeloproliferative neoplasm (MPN). An FRT-flanked neomycin resistance (neo) cassette was placed directly downstream of the second loxP511 site. The construct was electroporated into 129S6/SvEvTac-derived TC-1 embryonic stem (ES) cells. ES cells were injected into blastocysts and resulting chimeras were mated to C57BL/6 mice. Offspring were subsequently bred to ACTB:FLPe mice (Stock No. 005703) to remove the neo cassette and progeny were crossed to remove the Flpe-expressing transgene. Jak2^+/VF mice were bred to C57BL/6NCrl mice for at least 10 generations. Upon arrival at The Jackson Laboratory Repository, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6NJ oocytes (Stock No. 005304).

Control Suggestions

Wild-type from the colony

Approximate Controls

005304 C57BL/6NJ

Additional Information

Considerations for Choosing Controls

Selected References

Mullally A; Lane SW; Ball B; Megerdichian C; Okabe R; Al-Shahrour F; Paktinat M; Haydu JE; Housman E; Lord AM; Wernig G; Kharas MG; Mercher T; Kutok JL; Gilliland DG; Ebert BL. 2010. Physiological Jak2V617F expression causes a lethal myeloproliferative neoplasm with differential effects on hematopoietic stem and progenitor cells. Cancer Cell 17(6):584-96PubMed: 20541703 MGI: J:160883

View All References

Genetics

Jak2^tm1.2Ble

Allele Symbol: Jak2^tm1.2Ble

Allele Name	targeted mutation 1.2, Benjamin L Ebert
Allele Type	Targeted (Conditional ready (e.g. floxed))
Allele Synonym(s)	Jak2^VF; Jak2V617F
Gene Symbol and Name	Jak2, Janus kinase 2
Gene Synonym(s)
Strain of Origin	129S6/SvEvTac
Chromosome	19
Molecular Note	A loxP site was inserted upstream of exon 14 and a cassette, consisting of a loxP511site, a linker, an inverted loxP site, an inverted exon 14 containing a G1849T mutation, an inverted loxP511 site, and an FRT flanked neo selection cassette, was inserted downstream of exon 14 via homologous recombination. The neo cassette was removed by flp mediated recombination. Cre mediated recombination results in the removal of the endogenous exon 14 and the inversion of the mutated exon 14. The G1849T mutation results in a V617F substitution.

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

polycythemia vera

Research Areas By Phenotype

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

Immunology, Inflammation and Autoimmunity Research
- Intracellular Signaling Molecules
Cell Biology Research
- Signal Transduction
Research Tools
- Cre-lox System
  - loxP-flanked Sequences

Mammalian Phenotype Terms by Genotype

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

Genotype: Jak2^tm1.2Ble/Jak2^tm1.2Ble
involves: 129S6/SvEvTac * C57BL/6 * FVB/N

mortality/aging

prenatal lethality, complete penetrance
- unable to obtain any viable homozygotes, with the stage of prenatal lethality not specified

Genotype: Jak2^tm1.2Ble/Jak2⁺
involves: 129S6/SvEvTac * C57BL/6 * FVB/N

growth/size/body region phenotype

enlarged spleen

immune system phenotype

abnormal spleen morphology
- overall effacement of the normal architecture

abnormal spleen red pulp morphology
- marked erythroid and mild megakaryocytic hyperplasia in the splenic red pulp

enlarged spleen

increased leukocyte cell number

hematopoietic system phenotype

abnormal definitive hematopoiesis
- disproportional increase in the number of erythroid progenitors relative to other myeloid progenitor
- expansion of the megakaryocytic/erythroid progenitor (MEP) population

abnormal erythropoiesis
- increase in the number of erythroid precursors in the bone marrow and spleen
- marked erythroid hyperplasia in the splenic red pulp

abnormal hematopoietic system physiology
- gene set enrichment analysis indicates that hematopoietic differentiation in the LSK compartment is altered
- MEPs show EPO hypersensitivity

abnormal megakaryocyte morphology
- megakaryocytes with atypical nuclear features are present in the bone marrow

abnormal spleen morphology
- overall effacement of the normal architecture

abnormal spleen red pulp morphology
- marked erythroid and mild megakaryocytic hyperplasia in the splenic red pulp

enhanced megakaryocyte emperipolesis
- megakaryocytes with prominent emperipolesis are present in the bone marrow

enlarged spleen

extramedullary hematopoiesis
- prominent splenic extramedullary hematopoiesis

increased erythroid progenitor cell number

increased hematocrit

increased leukocyte cell number

increased megakaryocyte cell number
- mild hyperplasia in the splenic red pulp

mammalian phenotype

hematopoietic system phenotype
- Normal - despite the increase in megakaryocyte numbers no increases in platelet counts are detected

mortality/aging

premature death
- median survival is 146 days

neoplasm

increased hemolymphoid system tumor incidence
- all develop a myeloproliferative neoplasm
- Normal - however, acute leukemia is not detected
- these myeloproliferative neoplasms can be transplanted by transfer of either unfractionated bone marrow cells or LSK cells but not by transfer of MEP or granulocyte/macrophage progenitor cells

References

Mullally A; Lane SW; Ball B; Megerdichian C; Okabe R; Al-Shahrour F; Paktinat M; Haydu JE; Housman E; Lord AM; Wernig G; Kharas MG; Mercher T; Kutok JL; Gilliland DG; Ebert BL. 2010. Physiological Jak2V617F expression causes a lethal myeloproliferative neoplasm with differential effects on hematopoietic stem and progenitor cells. Cancer Cell 17(6):584-96PubMed: 20541703 MGI: J:160883

Additional - Jak2^tm1.2Ble related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Jak2-Alternate 2
- Sanger sequencing:Jak2 SEQ Alt 2
- Genotyping resources and troubleshooting
Dietary Information
- LabDiet® 5K54 formulation (4% fat)
Breeding Considerations

When maintaining a live colony, heterozygous mice may be bred to wild-type (noncarrier) mice from the colony or to C57BL/6NJ inbred mice (Stock No. 005304). The donating investigator reports that homozygous mice are not viable.
- Additional Breeding and Husbandry Support
Mating System
- Wild-type x Heterozygote
- Heterozygote x Wild-type
Citation
When using the Jak2^VF mouse strain in a publication, please cite the originating article(s) and include JAX stock #031658 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX18 (Maximum)

Pricing & Availability

Available

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Breeder Pair

Sex

Genotype

Price

Female
Male

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or wildtype for Jak2<tm1.2Ble>

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

The Jackson Laboratory's Genotype Promise

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.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

Credit for PRODUCTS or SERVICES

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.

Animal Care and Use for SERVICES

Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.

Also Known As:Jak2VF

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Jak2tm1.2Ble

Allele Symbol: Jak2tm1.2Ble

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Jak2tm1.2Ble/Jak2tm1.2Bleinvolves: 129S6/SvEvTac * C57BL/6 * FVB/N

mortality/aging

Genotype: Jak2tm1.2Ble/Jak2+involves: 129S6/SvEvTac * C57BL/6 * FVB/N

growth/size/body region phenotype

immune system phenotype

hematopoietic system phenotype

mammalian phenotype

mortality/aging

neoplasm

References

Additional - Jak2tm1.2Ble related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Citation

Animal Health Reports

Live Mouse

Breeder Pair

Cryorecovery - Pricing

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

Also Known As:Jak2^VF

Jak2^tm1.2Ble

Allele Symbol: Jak2^tm1.2Ble

Genotype: Jak2^tm1.2Ble/Jak2^tm1.2Ble
involves: 129S6/SvEvTac * C57BL/6 * FVB/N

Genotype: Jak2^tm1.2Ble/Jak2⁺
involves: 129S6/SvEvTac * C57BL/6 * FVB/N

Additional - Jak2^tm1.2Ble related