Overview

Mice that are homozygous null for Il15ra are lymphopenic as result of decreased proliferation and homing of lymphocytes to peripheral lymph nodes. Deficiencies are seen in levels of natural killer and T cells.

Donating Investigator

Averil Ma, University of California, San Francisco

Genetic overview

Genetic Background	Generation
	N?+N2F33 (2019-06-17 00:00:00)

Il15ra^tm1Ama

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Il15ra	interleukin 15 receptor, alpha chain

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Research Applications

Immunology, Inflammation and Autoimmunity Research
Research Tools
Hematological Research

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Base Price

Starting at:

$236.78 Domestic price for female

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Details

Detailed Description

Il15ra mediates the high-affinity binding of Il15, a pleiotropic cytokine implicated in the development of innate immune cells. Mice that are homozygous null for Il15ra are viable and fertile. They are lymphopenic as result of decreased proliferation and homing of lymphocytes to peripheral lymph nodes. As a result, marked hypocellularity of lymph nodes is observed. Deficiencies are seen in levels of natural killer cells, natural killer T cells, CD8⁺ T lymphocytes, TCR delta/gamma intraepithelial lymphocytes and memory phenotype CD8⁺ T cells.

Loss of IL15RA expression has also been shown to induce a functional oxidative shift in fast muscles, substantially increasing fatigue resistance and exercises capacity. Knockout mice run greater distances and have greater ambulatory activity than control animals.

Development

A targeting construct containing a phosphoglyceraldehyde driven neomycin resistance cassette flanked by loxP sequences and a phosphoglyceraldehyde driven thymidine kinase gene cassette was used to replace exons 2 and 3 of the Il15ra gene. The construct was electroporated into RW-4 ES ES cells. Selected ES cells were injected into C57BL/6 blastocysts.

Control Suggestions

101045 B6129SF2/J

Additional Information

Considerations for Choosing Controls

Selected References

Lodolce JP; Boone DL; Chai S; Swain RE; Dassopoulos T; Trettin S; Ma A. 1998. IL-15 receptor maintains lymphoid homeostasis by supporting lymphocyte homing and proliferation. Immunity 9(5):669-76PubMed: 9846488 MGI: J:51337

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Genetics

Il15ra^tm1Ama

Allele Symbol: Il15ra^tm1Ama

Allele Name	targeted mutation 1, Averil Ma
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Il15ra^tm1Ama; targeted mutation 1, Averil Ma
Gene Symbol and Name	Il15ra, interleukin 15 receptor, alpha chain
Gene Synonym(s)	expressed sequence AA690181; AA690181; CD215
Strain of Origin	129X1/SvJ
Chromosome	2
Molecular Note	A genomic fragment containing exons 2 and 3 was replaced by a neomycin resistance cassette. These sequences encode the ligand binding and proline/threonine rich extracellular domains. Northern blot analysis demonstrated that the transcript was not detectable in liver RNA from homozygous mice.
Mutations Made By	Averil Ma, University of California, San Francisco

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Genotype: Il15ra^tm1Ama related

Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - B, T, and NK cell deficiency
- Growth Factors/Receptors/Cytokines
Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - NK Cell Deficiency
Hematological Research
- Immunological 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: Il15ra^tm1Ama/Il15ra^tm1Ama
involves: 129X1/SvJ

cellular phenotype

decreased T cell proliferation
- compared to donor wild-type cells
- donor CD4+ and CD8+ T cells transplanted into irradiated wild-type mice exhibit reduced cell-cycle progression compared to donor wild-type cellsdonor CD4+ and CD8+ T cells transplanted into irradiated wild-type mice exhibit reduced cell-cycle progression compared to donor wild-type cells
- Normal - however, stimulation of TCR-activated CD8+ T cells with 500 ng/mL IL15 induces normal proliferation
- TCR-activated CD8+ T cells stimulated with 5 ng/mL IL15 exhibit little if any proliferation while stimulation with 50 ng/mL induces reduced proliferation compared to similarly treated wild-type cells

immune system phenotype

abnormal NK cell physiology
- NK cells generated in vitro do not express Ly-49 receptors as normal NK cells do; NK cells differentiated in vivo from transplanted mutant splenic and BM cells show much lower expression of Ly-49 than wild-type NK cells

decreased CD8-positive, alpha-beta T cell number
- mice exhibit a reduction in CD8+ T cells compared to in wild-type mice

decreased CD8-positive, gamma-delta intraepithelial T cell number
- marked reduction

decreased memory T cell number
- mice exhibit a reduction in CD44^highIL23beta+CD8+ memory T cells compared to in wild-type mice

decreased NK cell number
- Normal - NK cells
- Normal - however, when spleen and BM progenitors are cultured with appropriate factors (Il-7, SCF, flt3) followed by Il-15, they can differentiate into functional NK cells, if transplanted into wild-type recipients, spleen and BM cells can differentiate in vivo to NK cells
- in 6 to 12 week-old mice, percentages of NK cells in spleen and bone marrow (BM) or mutants are extremely low
- mice exhibit a reduction in splenic NK cells compared to in wild-type mice

decreased NK T cell number
- mice exhibit a reduction in NKT and thymic NKT cells compared to in wild-type mice

decreased T cell proliferation
- compared to donor wild-type cells
- donor CD4+ and CD8+ T cells transplanted into irradiated wild-type mice exhibit reduced cell-cycle progression compared to donor wild-type cellsdonor CD4+ and CD8+ T cells transplanted into irradiated wild-type mice exhibit reduced cell-cycle progression compared to donor wild-type cells
- Normal - however, stimulation of TCR-activated CD8+ T cells with 500 ng/mL IL15 induces normal proliferation
- TCR-activated CD8+ T cells stimulated with 5 ng/mL IL15 exhibit little if any proliferation while stimulation with 50 ng/mL induces reduced proliferation compared to similarly treated wild-type cells

impaired natural killer cell mediated cytotoxicity
- mice have no cytolytic NK activity

hematopoietic system phenotype

abnormal NK cell physiology
- NK cells generated in vitro do not express Ly-49 receptors as normal NK cells do; NK cells differentiated in vivo from transplanted mutant splenic and BM cells show much lower expression of Ly-49 than wild-type NK cells

decreased CD8-positive, alpha-beta T cell number
- mice exhibit a reduction in CD8+ T cells compared to in wild-type mice

decreased CD8-positive, gamma-delta intraepithelial T cell number
- marked reduction

decreased memory T cell number
- mice exhibit a reduction in CD44^highIL23beta+CD8+ memory T cells compared to in wild-type mice

decreased NK cell number
- Normal - NK cells
- Normal - however, when spleen and BM progenitors are cultured with appropriate factors (Il-7, SCF, flt3) followed by Il-15, they can differentiate into functional NK cells, if transplanted into wild-type recipients, spleen and BM cells can differentiate in vivo to NK cells
- in 6 to 12 week-old mice, percentages of NK cells in spleen and bone marrow (BM) or mutants are extremely low
- mice exhibit a reduction in splenic NK cells compared to in wild-type mice

decreased NK T cell number
- mice exhibit a reduction in NKT and thymic NKT cells compared to in wild-type mice

decreased T cell proliferation
- compared to donor wild-type cells
- donor CD4+ and CD8+ T cells transplanted into irradiated wild-type mice exhibit reduced cell-cycle progression compared to donor wild-type cellsdonor CD4+ and CD8+ T cells transplanted into irradiated wild-type mice exhibit reduced cell-cycle progression compared to donor wild-type cells
- Normal - however, stimulation of TCR-activated CD8+ T cells with 500 ng/mL IL15 induces normal proliferation
- TCR-activated CD8+ T cells stimulated with 5 ng/mL IL15 exhibit little if any proliferation while stimulation with 50 ng/mL induces reduced proliferation compared to similarly treated wild-type cells

impaired natural killer cell mediated cytotoxicity
- mice have no cytolytic NK activity

References

Lodolce JP; Boone DL; Chai S; Swain RE; Dassopoulos T; Trettin S; Ma A. 1998. IL-15 receptor maintains lymphoid homeostasis by supporting lymphocyte homing and proliferation. Immunity 9(5):669-76PubMed: 9846488 MGI: J:51337

Additional References

Zhou X; Yu J; Cheng X; Zhao B; Manyam GC; Zhang L; Schluns K; Li P; Wang J; Sun SC. 2019. The deubiquitinase Otub1 controls the activation of CD8(+) T cells and NK cells by regulating IL-15-mediated priming. Nat Immunol 20(7):879-889PubMed: 31182807 MGI: J:278896

Additional - Il15ra^tm1Ama related

Technical Support

Contact Technical Support

Genotyping Protocols
- Standard PCR:Il15ra^tm1Ama
- Genotyping resources and troubleshooting
Dietary Information
- LabDiet® 5K52 formulation (6% fat)
Breeding Considerations

This mutant originated on a B6;129 background. The donating investigator maintained it as a heterozygote using intercrosses. Coat color expected from breeding:Albino
- Additional Breeding and Husbandry Support
Mating System
- Homozygote x Homozygote
Citation
When using the B6;129X1-Il15ra^tm1Ama/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #003723 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX11 (Maximum)

Pricing & Availability

Available

Domestic
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Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Heterozygous for Il15ra<tm1Ama>

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.

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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.

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Il15ratm1Ama

Allele Symbol: Il15ratm1Ama

Disease Terms

Research Areas By Genotype

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

Genotype: Il15ratm1Ama related

Mammalian Phenotype Terms by Genotype

Genotype: Il15ratm1Ama/Il15ratm1Amainvolves: 129X1/SvJ

cellular phenotype

immune system phenotype

hematopoietic system phenotype

References

Additional References

Additional - Il15ratm1Ama related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Citation

Animal Health Reports

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Il15ra^tm1Ama

Allele Symbol: Il15ra^tm1Ama

Genotype: Il15ra^tm1Ama related

Genotype: Il15ra^tm1Ama/Il15ra^tm1Ama
involves: 129X1/SvJ

Additional - Il15ra^tm1Ama related