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

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

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

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
- about a 2-fold increase in apoptotic thymocytes is seen from E14 - E17
- 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
- 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

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

absent B cells

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

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

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

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

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

thymus hypoplasia

endocrine/exocrine gland phenotype

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

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

thymus hypoplasia

immune system phenotype

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

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

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
- about a 2-fold increase in apoptotic thymocytes is seen from E14 - E17
- 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
- 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

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

absent B cells

absent lymph nodes

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

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

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

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

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

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

thymus hypoplasia

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

hematopoietic system phenotype

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

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

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

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

immune system phenotype

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

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

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

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

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

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
- 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

immune system phenotype

abnormal B cell morphology

abnormal immune system physiology

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

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

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

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

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

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

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

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

small lymph nodes
- peripheral lymph nodes are nearly undetectable

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

small thymus

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

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

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

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

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

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

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

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

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

small thymus

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

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

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 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

abnormal dendritic cell physiology
- bone marrow-derived dendritic cells overproduce IL12 and IL10
- in culture, dendritic cells are resistant to cytokine withdrawal-induced apoptosis
- 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

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 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

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

hematopoietic system 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

abnormal dendritic cell morphology

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 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

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

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

Cryo Recovery

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Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous for Jak3<tm1Ljb>

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Frozen Mouse Embryo	B6;129S4-Jak3<tm1Ljb>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	B6;129S4-Jak3<tm1Ljb>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	B6;129S4-Jak3<tm1Ljb>/J Frozen Embryos	$3373.50
Frozen Mouse Embryo	B6;129S4-Jak3<tm1Ljb>/J Frozen Embryos	$3373.50

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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

hematopoietic system phenotype

immune system phenotype

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

cellular phenotype

endocrine/exocrine gland phenotype

immune system phenotype

hematopoietic system phenotype

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

cellular 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

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

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
involves: 129S4/SvJae * C57BL/6

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

Additional - Jak3^tm1Ljb related