Overview

Mice homozygous for Jak3^tm1Ljb have blocked B cell development at pre-B resulting in a significant decrease in peripheral IgM⁺ B cells. Proliferative responses to mitogenic signals are defective and Il2 receptor signaling is blocked. The overall phenotype results in a severely immunocompromised mouse.

Donating Investigator

Dr. Leslie Berg, University of Massachusetts Medical School

Genetic overview

Genetic Background	Generation

Jak3^tm1Ljb

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Jak3	Janus kinase 3

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Research Applications

Immunology, Inflammation and Autoimmunity Research
Research Tools
Mouse/Human Gene Homologs

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice homozygous for the Jak3^tm1Ljb mutation are viable and fertile. B cell development is blocked at pre-B resulting in a significant decrease in peripheral IgM⁺ B cells. The thymus is small but T cell development is relatively normal. There are increased numbers of CD4⁺ Cd8^- cells in some homozygotes. Proliferative responses to mitogenic signals are defective and Il2 receptor signaling is blocked. The overall phenotype results in a severely immunocompromised mouse.

Control Suggestions

Approximate Controls

101045 B6129SF2/J

Additional Information

Considerations for Choosing Controls

Selected References

Thomis DC; Gurniak CB; Tivol E; Sharpe AH; Berg LJ. 1995. Defects in B lymphocyte maturation and T lymphocyte activation in mice lacking Jak3. Science 270(5237):794-7PubMed: 7481767 MGI: J:29722

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Genetics

Jak3^tm1Ljb

Allele Symbol: Jak3^tm1Ljb

Allele Name	targeted mutation 1, Leslie J Berg
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Jak-3-; Jak3^-
Gene Symbol and Name	Jak3, Janus kinase 3
Gene Synonym(s)
Strain of Origin	129S4/SvJae
Chromosome	8
Molecular Note	A neomycin resistance cassette replaced a 0.6 kb fragment of the gene, which contains sequences encoding subdomains I to IV of the kinase domain. Protein immunoblots of lysates from bone marrow, spleen, and thymus showed no targeted protein.
Mutations Made By	Dr. Leslie Berg, University of Massachusetts Medical School

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-positive, Nk cell-positive

Research Areas By Phenotype

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

Genotype: Jak3^tm1Ljb related

Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - B, T, and NK cell deficiency
- Intracellular Signaling Molecules
Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - B cell deficiency
- Cancer Research
  - B, T, and NK cell deficiency, xenograft/transplant host
Mouse/Human Gene Homologs
- severe combined immunodeficiency disease, autosomal recessive, T-negative/ B-positive type

Mammalian Phenotype Terms by Genotype

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

Genotype: Jak3^tm1Ljb/Jak3^tm1Ljb
involves: 129S4/SvJae

cellular phenotype

decreased T cell proliferation
- decrease in thymocyte proliferation in response to CD3 plus CD28 stimulation compared to wild-type
- the proliferative response of splenic T cells in response to T cell receptor plus CD28 stimulation is virtually absent

hematopoietic system phenotype

abnormal spleen white pulp morphology
- numerous megakaryoctes are present
- the white pulp is replaced with a collection of large cells with euchromatic nuclei that are CD3+

abnormal T cell activation
- CD4+ cells that are present show an activated phenotype
- CD4+ T cells resemble activated or memory T cells

abnormal T cell differentiation
- from E15 - E17, T cell maturation appears to be delayed by about 1 day compared to age-matched heterozygous littermates
- most intrathymically injected cells arrest at the CD44+ CD25- double negativeprogenitor cell stage
- the proportion of pro-T cells is increased about 3-fold and fewer cells in transition between pre-T and late pre-T cell stages are found
- Normal - however, by E18 T cell maturation in homozygous mice has caught up to that of their heterozygous littermates
- about a 2-fold increase in apoptotic thymocytes is seen from E14 - E17
- both pro-T and pre-T cells have increased CD25 expression
- intrathymically injected bone marrow cells show extremely limited ability to reconstitute T cell development especially when in competition with heterozygous or wild-type cells

abnormal myelopoiesis
- increase in the number of myeloid progenitor cells in the peripheral blood and bone marrow

abnormal thymus cell ratio
- increase in the ratio of CD4+ to CD8+ cells

decreased T cell proliferation
- the proliferative response of splenic T cells in response to T cell receptor plus CD28 stimulation is virtually absent
- decrease in thymocyte proliferation in response to CD3 plus CD28 stimulation compared to wild-type

decreased thymocyte number
- in adult mice, there is about a 20-fold reduction in thymocyte numbers
- at E14 - E15, thymocytes are virtually undetectable
- at E14 only about 200 Thy+ cells are present in the thymus compared to around 20,000 in age-matched heterozygous littermates
- despite the deficit in progenitors, the rate of thymocyte expansion between E14 and E18 and differentiation of thymic progenitors into pro-T cells are similar to that of heterozygous littermates

absent B cells

decreased lymphocyte cell number
- lymphopenia is seen in peripheral and bone marrow smears
- at 6-12 months of age, lymphocyte numbers in whole blood suspensions are decreased

enlarged spleen
- seen in all mice over 5 months of age
- may be seen in some mice by as early as 4 months of age

increased monocyte cell number
- at 6 - 12 months of age in the bone marrow and spleen

abnormal spleen morphology
- the general architecture of the spleen is severely disrupted

abnormal T cell physiology
- thymocytes produce less IL12 and IL13 in response to anti-CD3 plus anti-CD28-stimulation compared to wild-type controls
- splenic T cells secrete less IL12 in response to T cell receptor plus CD28 stimulation

abnormal erythropoiesis
- slight decrease in the number of erythroid progenitors in the bone marrow

increased leukocyte cell number
- at 6-12 months of age, a profound increase in large granular cells is seen in the peripheral blood and spleen
- these large granular cells consist of 2 populations; cells of the neutrophilic lineage and cells of the monocytic lineage

abnormal leukocyte morphology
- large increase in the number of cells classified as myeloid or premonocytic

increased neutrophil cell number
- significantly higher numbers of both segmented and band neutrophils

thymus hypoplasia

endocrine/exocrine gland phenotype

decreased thymocyte number
- at E14 - E15, thymocytes are virtually undetectable
- at E14 only about 200 Thy+ cells are present in the thymus compared to around 20,000 in age-matched heterozygous littermates
- despite the deficit in progenitors, the rate of thymocyte expansion between E14 and E18 and differentiation of thymic progenitors into pro-T cells are similar to that of heterozygous littermates
- in adult mice, there is about a 20-fold reduction in thymocyte numbers

abnormal thymus cell ratio
- increase in the ratio of CD4+ to CD8+ cells

thymus hypoplasia

immune system phenotype

decreased thymocyte number
- at E14 - E15, thymocytes are virtually undetectable
- at E14 only about 200 Thy+ cells are present in the thymus compared to around 20,000 in age-matched heterozygous littermates
- despite the deficit in progenitors, the rate of thymocyte expansion between E14 and E18 and differentiation of thymic progenitors into pro-T cells are similar to that of heterozygous littermates
- in adult mice, there is about a 20-fold reduction in thymocyte numbers

enlarged spleen
- seen in all mice over 5 months of age
- may be seen in some mice by as early as 4 months of age

abnormal spleen white pulp morphology
- numerous megakaryoctes are present
- the white pulp is replaced with a collection of large cells with euchromatic nuclei that are CD3+

abnormal T cell differentiation
- the proportion of pro-T cells is increased about 3-fold and fewer cells in transition between pre-T and late pre-T cell stages are found
- about a 2-fold increase in apoptotic thymocytes is seen from E14 - E17
- most intrathymically injected cells arrest at the CD44+ CD25- double negativeprogenitor cell stage
- both pro-T and pre-T cells have increased CD25 expression
- from E15 - E17, T cell maturation appears to be delayed by about 1 day compared to age-matched heterozygous littermates
- Normal - however, by E18 T cell maturation in homozygous mice has caught up to that of their heterozygous littermates
- intrathymically injected bone marrow cells show extremely limited ability to reconstitute T cell development especially when in competition with heterozygous or wild-type cells

increased leukocyte cell number
- these large granular cells consist of 2 populations; cells of the neutrophilic lineage and cells of the monocytic lineage
- at 6-12 months of age, a profound increase in large granular cells is seen in the peripheral blood and spleen

abnormal spleen morphology
- the general architecture of the spleen is severely disrupted

abnormal T cell physiology
- splenic T cells secrete less IL12 in response to T cell receptor plus CD28 stimulation
- thymocytes produce less IL12 and IL13 in response to anti-CD3 plus anti-CD28-stimulation compared to wild-type controls

abnormal T cell activation
- CD4+ cells that are present show an activated phenotype
- CD4+ T cells resemble activated or memory T cells

decreased lymphocyte cell number
- lymphopenia is seen in peripheral and bone marrow smears
- at 6-12 months of age, lymphocyte numbers in whole blood suspensions are decreased

increased neutrophil cell number
- significantly higher numbers of both segmented and band neutrophils

chronic inflammation
- widespread infiltration of the lungs, kidneys, and liver with mononuclear cells

decreased T cell proliferation
- decrease in thymocyte proliferation in response to CD3 plus CD28 stimulation compared to wild-type
- the proliferative response of splenic T cells in response to T cell receptor plus CD28 stimulation is virtually absent

absent lymph nodes

abnormal thymus cell ratio
- increase in the ratio of CD4+ to CD8+ cells

increased monocyte cell number
- at 6 - 12 months of age in the bone marrow and spleen

thymus hypoplasia

abnormal leukocyte morphology
- large increase in the number of cells classified as myeloid or premonocytic

abnormal myelopoiesis
- increase in the number of myeloid progenitor cells in the peripheral blood and bone marrow

absent B cells

growth/size/body region phenotype

enlarged spleen
- may be seen in some mice by as early as 4 months of age
- seen in all mice over 5 months of age

Genotype: Jak3^tm1Ljb/Jak3⁺
involves: 129S4/SvJae

immune system phenotype

increased leukocyte cell number
- these large granular cells consist of 2 populations; cells of the neutrophilic lineage and cells of the monocytic lineage
- at 6-12 months of age, a profound increase in large granular cells is seen in the peripheral blood and spleen

decreased lymphocyte cell number
- at 6-12 months of age, lymphocyte numbers in whole blood suspensions are decreased
- lymphopenia is seen in peripheral and bone marrow smears

abnormal leukocyte morphology
- slight increase in the number of cells classified as myeloid or premonocytic

increased monocyte cell number
- at 6 - 12 months of age in the bone marrow and spleen

increased neutrophil cell number
- significantly higher numbers of both segmented and band neutrophils

hematopoietic system phenotype

increased leukocyte cell number
- these large granular cells consist of 2 populations; cells of the neutrophilic lineage and cells of the monocytic lineage
- at 6-12 months of age, a profound increase in large granular cells is seen in the peripheral blood and spleen

decreased lymphocyte cell number
- lymphopenia is seen in peripheral and bone marrow smears
- at 6-12 months of age, lymphocyte numbers in whole blood suspensions are decreased

increased monocyte cell number
- at 6 - 12 months of age in the bone marrow and spleen

increased neutrophil cell number
- significantly higher numbers of both segmented and band neutrophils

abnormal leukocyte morphology
- slight increase in the number of cells classified as myeloid or premonocytic

The following phenotype relates to a compound genotype created using this strain

Genotype: Jak3^tm1Ljb/Jak3^tm1Ljb
B6;129S4-Jak3/J

cellular phenotype

abnormal dendritic cell differentiation
- Normal - however, bone marrow precursors in vitro show a similar capacity to generate immature dendritic cells compared to wild-type controls
- splenic dendritic cells express higher levels of activation markers compared to cells from wild-type controls

immune system phenotype

abnormal dendritic cell physiology
- when bone marrow-derived dendritic cells are used in an adoptive transfer model the proportion of IFNG-producing cells is increased compared to when wild-type cells are used
- bone marrow-derived dendritic cells overproduce IL12 and IL10
- in culture, dendritic cells are resistant to cytokine withdrawal-induced apoptosis

abnormal splenic cell ratio
- decrease in the proportion and absolute number of CD11c+ dendritic, CD4+, and CD8+ cells in the spleen
- Normal - however, the frequency plasmacytoid dendritic cells is not significantly different from wild-type controls
- reduced numbers of splenocytes

decreased CD8-positive, alpha-beta T cell number
- decrease in the proportion and absolute number of CD8+ cells in the spleen

decreased myeloid dendritic cell number
- Normal - however, the frequency plasmacytoid dendritic cells in the spleen is not significantly different from wild-type controls
- the proportion and absolute number of CD11c+ dendritic cells is decreased in the spleen

abnormal dendritic cell differentiation
- Normal - however, bone marrow precursors in vitro show a similar capacity to generate immature dendritic cells compared to wild-type controls
- splenic dendritic cells express higher levels of activation markers compared to cells from wild-type controls

abnormal dendritic cell morphology

decreased CD4-positive, alpha beta T cell number
- decrease in the proportion and absolute number of CD4+ cells in the spleen

hematopoietic system phenotype

abnormal splenic cell ratio
- decrease in the proportion and absolute number of CD11c+ dendritic, CD4+, and CD8+ cells in the spleen
- Normal - however, the frequency plasmacytoid dendritic cells is not significantly different from wild-type controls
- reduced numbers of splenocytes

decreased myeloid dendritic cell number
- Normal - however, the frequency plasmacytoid dendritic cells in the spleen is not significantly different from wild-type controls
- the proportion and absolute number of CD11c+ dendritic cells is decreased in the spleen

decreased CD4-positive, alpha beta T cell number
- decrease in the proportion and absolute number of CD4+ cells in the spleen

decreased CD8-positive, alpha-beta T cell number
- decrease in the proportion and absolute number of CD8+ cells in the spleen

abnormal dendritic cell differentiation
- Normal - however, bone marrow precursors in vitro show a similar capacity to generate immature dendritic cells compared to wild-type controls
- splenic dendritic cells express higher levels of activation markers compared to cells from wild-type controls

abnormal dendritic cell morphology

Genotype: Jak3^tm1Ljb/Jak3^tm1Ljb
involves: 129S4/SvJae * C57BL/6

cellular phenotype

decreased T cell proliferation
- mitogen-induced thymocyte and splenic T cell proliferation responses are significantly reduced compared to wild-type cells

endocrine/exocrine gland phenotype

small thymus

thymus hypoplasia
- total cell numbers range from 0.5 to 10% of wild-type controls
- Normal - however, the proportion of different cell types is similar to controls

immune system phenotype

abnormal B cell morphology

arrested B cell differentiation
- Normal - however, total bone marrow cell numbers are similar to wild-type controls
- profound block in B cell development at the pre-B cell stage

decreased immature B cell number
- Normal - however, no significant decrease in the number of CD43+ CD45R+ cells is detected
- decreased numbers of CD43- CD45R+ cells are detected in the bone marrow or spleen

abnormal response to infection
- the LPS-induced proliferation response of spleen cells is significantly reduced

abnormal splenic cell ratio
- spleens contain an increased percentage of Thy1- CD45R- Mac1- cells

decreased T cell proliferation
- mitogen-induced thymocyte and splenic T cell proliferation responses are significantly reduced compared to wild-type cells

small lymph nodes
- peripheral lymph nodes are nearly undetectable

abnormal leukocyte physiology
- Normal - however, chemotactic responses towards CCL5, CCL11 and CCL14 are not significantly different from heterozygous controls
- decrease in the chemotactic response of thymocytes towards CCL25 and CXCL12

abnormal T cell activation
- most of the splenic T cells express markers of activation and are larger than wild-type splenic T cells
- splenic T cells stimulated with anti-CD3 plus anti-CD28 secrete significantly less IL-2

decreased IgG level
- serum IgG levels appear to be lower in mice at 3 months of age
- Normal - however, in younger mice serum Ig levels are similar to wild-type

small Peyer's patches
- Peyer's patches are almost undetectable

small thymus

lymph node hypoplasia
- the ratio of CD4+ to CD8+ cells is increase with more than 60% of the cells being CD4+ and less than 5% being CD8+
- peripheral lymph nodes contain only about 2% the normal number of cells

spleen hypoplasia
- total spleen cell numbers range from 10 to 500% of wild-type controls

decreased mature B cell number
- peritoneal lavage cells contain significantly fewer CD45R+ IgM+ cells
- virtually no CD45R+ IgM+ cells are detected in the bone marrow or spleen

thymus hypoplasia
- total cell numbers range from 0.5 to 10% of wild-type controls
- Normal - however, the proportion of different cell types is similar to controls

abnormal immune system physiology

abnormal lymphocyte physiology
- cells that do migrate towards CCL25 and CXCL12 are enriched for hematopoietic progenitors
- decrease in the chemotactic response of bone marrow cells towards CCL25 and CXCL12

hematopoietic system phenotype

abnormal B cell morphology

abnormal leukocyte physiology
- decrease in the chemotactic response of thymocytes towards CCL25 and CXCL12
- Normal - however, chemotactic responses towards CCL5, CCL11 and CCL14 are not significantly different from heterozygous controls

abnormal lymphocyte physiology
- cells that do migrate towards CCL25 and CXCL12 are enriched for hematopoietic progenitors
- decrease in the chemotactic response of bone marrow cells towards CCL25 and CXCL12

decreased mature B cell number
- virtually no CD45R+ IgM+ cells are detected in the bone marrow or spleen
- peritoneal lavage cells contain significantly fewer CD45R+ IgM+ cells

abnormal T cell activation
- splenic T cells stimulated with anti-CD3 plus anti-CD28 secrete significantly less IL-2
- most of the splenic T cells express markers of activation and are larger than wild-type splenic T cells

decreased IgG level
- serum IgG levels appear to be lower in mice at 3 months of age
- Normal - however, in younger mice serum Ig levels are similar to wild-type

decreased T cell proliferation
- mitogen-induced thymocyte and splenic T cell proliferation responses are significantly reduced compared to wild-type cells

arrested B cell differentiation
- Normal - however, total bone marrow cell numbers are similar to wild-type controls
- profound block in B cell development at the pre-B cell stage

small thymus

spleen hypoplasia
- total spleen cell numbers range from 10 to 500% of wild-type controls

abnormal splenic cell ratio
- spleens contain an increased percentage of Thy1- CD45R- Mac1- cells

thymus hypoplasia
- Normal - however, the proportion of different cell types is similar to controls
- total cell numbers range from 0.5 to 10% of wild-type controls

decreased immature B cell number
- decreased numbers of CD43- CD45R+ cells are detected in the bone marrow or spleen
- Normal - however, no significant decrease in the number of CD43+ CD45R+ cells is detected

References

Thomis DC; Gurniak CB; Tivol E; Sharpe AH; Berg LJ. 1995. Defects in B lymphocyte maturation and T lymphocyte activation in mice lacking Jak3. Science 270(5237):794-7PubMed: 7481767 MGI: J:29722

Additional References

Antov A; Yang L; Vig M; Baltimore D; Van Parijs L. 2003. Essential role for STAT5 signaling in CD25+CD4+ regulatory T cell homeostasis and the maintenance of self-tolerance. J Immunol 171(7):3435-41PubMed: 14500638 MGI: J:85631
Soldevila G; Licona I; Salgado A; Ramirez M; Chavez R; Garcia-Zepeda E. 2004. Impaired chemokine-induced migration during T-cell development in the absence of Jak 3. Immunology 112(2):191-200PubMed: 15147562 MGI: J:90510

Additional - Jak3^tm1Ljb related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Jak3
- Genotyping resources and troubleshooting
Breeding Considerations

Colony is currently maintained homozygote x homozygote. Expected coat color from breeding is black or agouti.
- Additional Breeding and Husbandry Support
Appearance
- black
  Related Genotype: a/a
Citation
When using the B6;129S4-Jak3^tm1Ljb/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #002852 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

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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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Email: TechTran@jax.org

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Control Suggestions

Approximate Controls

Additional Information

Selected References

Jak3tm1Ljb

Allele Symbol: Jak3tm1Ljb

Disease Terms

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

Research Areas By Phenotype

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

Genotype: Jak3tm1Ljb related

Mammalian Phenotype Terms by Genotype

Genotype: Jak3tm1Ljb/Jak3tm1Ljbinvolves: 129S4/SvJae

cellular phenotype

hematopoietic system phenotype

endocrine/exocrine gland phenotype

immune system phenotype

growth/size/body region phenotype

Genotype: Jak3tm1Ljb/Jak3+involves: 129S4/SvJae

immune system phenotype

hematopoietic system phenotype

Genotype: Jak3tm1Ljb/Jak3tm1LjbB6;129S4-Jak3/J

cellular phenotype

immune system phenotype

hematopoietic system phenotype

Genotype: Jak3tm1Ljb/Jak3tm1Ljbinvolves: 129S4/SvJae * C57BL/6

cellular phenotype

endocrine/exocrine gland phenotype

immune system phenotype

hematopoietic system phenotype

References

Additional References

Additional - Jak3tm1Ljb related

Genotyping Protocols

Breeding Considerations

Appearance

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

Licensing Information

Jak3^tm1Ljb

Allele Symbol: Jak3^tm1Ljb

Genotype: Jak3^tm1Ljb related

Genotype: Jak3^tm1Ljb/Jak3^tm1Ljb
involves: 129S4/SvJae

Genotype: Jak3^tm1Ljb/Jak3⁺
involves: 129S4/SvJae

Genotype: Jak3^tm1Ljb/Jak3^tm1Ljb
B6;129S4-Jak3/J

Genotype: Jak3^tm1Ljb/Jak3^tm1Ljb
involves: 129S4/SvJae * C57BL/6

Additional - Jak3^tm1Ljb related