Overview

This Tbx21 (or T-bet) knock-out mutant mouse strain represents a model that may be useful in studies of acute and chronic human asthma, chronic intestinal inflammation, metabolic physiology and obesity-associated insulin resistance.

Donating Investigator

Dr. Laurie H. Glimcher, Dana Farber Cancer Institute

Genetic overview

Genetic Background	Generation

Tbx21^tm1Glm

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Tbx21	T-box 21

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Research Applications

Immunology, Inflammation and Autoimmunity Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

The Tbx21 gene encodes a transcription factor that controls expression of interferon-gamma and is involved in Th1 cell lineage development. Mice that are homozygous for this targeted mutation of Tbx21, in which a NEO cassette replaces 2 Kb of sequence (exon 1 and flanking sequence), are viable and fertile. No gene product (mRNA or protein) is detected in isolated lymph node T-cells by Northern or Western blot analysis. T cells from the homozygotes do not produce the TH1 type cytokine, interferon-gamma, and secrete elevated levels of TH2 type cytokines in vitro to TCR cross-linking and in vivo to protein antigen immunization. Additionally, mice homozygous for the targeted mutation on the BALB/c genetic background are susceptible to Leishmania major infections. Without induced sensitization or challenge, female homozygotes display airway hyper responsiveness (AHR) with resulting airway remodeling similar to characteristics of asthma. Histological analysis of lung from female homozygous mice, aged 4 to 6 weeks, reveals eosinophil and lymphocyte infiltration of peribronchial and perivenular tissue, thickening of the subepithelial collagen layer, and increased numbers of myofibroblast cells in bronchial tissue. Bronchial alveolar lavage fluid contains elevated levels of TGF-beta1, TNF-alpha, IL-4 and IL-13. Mice heterozygous for the targeted mutation display an intermediate phenotype. Homozygous male mice, at 8 weeks to 28 weeks of age, weigh more than wildtype controls. Although food intake on a low fat diet was similar for all genotypes, homozygous mice exhibit a lower food intake on a high fat diet compare to wildtype controls. Homozygotes also display increased intra-abdominal or visceral adipose tissue mass and increased adipocyte size when compared to controls. Homozygotes at 8 weeks and 6 months of age exhibit lower fasting and fed serum insulin levels, better glucose tolerance and enhanced insulin sensitivity than wildtype controls. Adipose tissue in homozygotes have fewer CD45+, CD4+, CD8+, and NK cells and reduced cytokine secretion.

Development

A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt 2 Kb of sequence encoding exon 1 and flanking sequence. The construct was electroporated into 129S6/SvEvTac derived TC1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to BALB/c mice, and then backcrossed to BALB/c for 8 generations.

Control Suggestions

000651 BALB/cJ

Additional Information

Considerations for Choosing Controls

Selected References

Finotto S; Neurath MF; Glickman JN; Qin S; Lehr HA; Green FH; Ackerman K; Haley K; Galle PR; Szabo SJ; Drazen JM; De Sanctis GT; Glimcher LH. 2002. Development of spontaneous airway changes consistent with human asthma in mice lacking T-bet. Science 295(5553):336-8PubMed: 11786643 MGI: J:73832

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Genetics

Tbx21^tm1Glm

Allele Symbol: Tbx21^tm1Glm

Allele Name	targeted mutation 1, Laurie H Glimcher
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	targeted mutation 1, Laurie H Glimcher; Tbx21^tm1Glm
Gene Symbol and Name	Tbx21, T-box 21
Gene Synonym(s)	T-PET; TBLYM; T-bet; TBET; TBT1; Tbet; Tblym
Strain of Origin	129S6/SvEvTac
Chromosome	11
Molecular Note	A neomycin selection cassette was used to replace a 2 kb region containing exon 1 and its flanking sequence. An absence of mRNA and protein were observed in T cells isolated from the lymph nodes of homozygous mutant mice by Northern blot and Western blot analysis, respectively.
Mutations Made By	Dr. Laurie Glimcher, Dana Farber Cancer Institute

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).

asthma

Research Areas By Genotype

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

Genotype: Tbx21^tm1Glm related

Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - Asthma
- Inflammation
  - Asthma

Mammalian Phenotype Terms by Genotype

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

Genotype: Tbx21^tm1Glm/Tbx21^tm1Glm
involves: 129S6/SvEvTac * C57BL/6

hematopoietic system phenotype

abnormal CD8-positive, alpha-beta cytotoxic T cell morphology
- mutants have normal numbers of Ifng-producing CD8 T cells; as well, unexpectedly, mutant CD8 T cells produce equivalent levels of Ifng to wild-type

abnormal immunoglobulin level
- normal mixed response to protein antigen immunization is altered; after TNP-KLH treatment mice produced decreased IgG2a and very slightly increased IgG1 compared to controls at day 12

abnormal NK cell physiology
- splenic NK cells from mutants produce less Ifng in response to Il-12 or Il-18 than NK cells from wild-type

abnormal T-helper 1 cell differentiation
- differentiation of CD4 T cells into helper T cell subsets is impaired or altered; cells fail to differentiate into Th1 lineage and default to Th2 fate

decreased T helper 1 cell number
- number of Ifng producing cells (Th1) decreases while Th2 cells producing Il-4 and Il-5 increase in number

impaired natural killer cell mediated cytotoxicity
- NK cells from mutants are impaired in ability to lyse YAC-1 cells compared to wild-type

increased natural killer cell mediated cytotoxicity
- NK cells from mutants treated with poly(I:C) for activation lyse tumor cell targets equivalently to wild-type NK cells

increased T-helper 2 cell number
- number of Ifng producing cells (Th1) decreases while Th2 cells producing Il-4 and Il-5 increase in number

immune system phenotype

abnormal CD8-positive, alpha-beta cytotoxic T cell morphology
- mutants have normal numbers of Ifng-producing CD8 T cells; as well, unexpectedly, mutant CD8 T cells produce equivalent levels of Ifng to wild-type

abnormal cytokine level
- increased amount of TGFb is found in bronchial alveolar lavage (BAL) fluid compared to wild-type

abnormal immunoglobulin level
- normal mixed response to protein antigen immunization is altered; after TNP-KLH treatment mice produced decreased IgG2a and very slightly increased IgG1 compared to controls at day 12

abnormal interleukin level
- increased amounts of Il-4 and Il-13 are found in BAL fluid; Il-5 levels are high in mutants and do not increase with allergen challenge as wild-type levels do

abnormal NK cell physiology
- splenic NK cells from mutants produce less Ifng in response to Il-12 or Il-18 than NK cells from wild-type

abnormal T-helper 1 cell differentiation
- differentiation of CD4 T cells into helper T cell subsets is impaired or altered; cells fail to differentiate into Th1 lineage and default to Th2 fate

abnormal tumor necrosis factor level
- increased amount of TNFa is found in bronchial alveolar lavage (BAL) fluid compared to wild-type

decreased interferon-gamma secretion
- anti-CD3 and -CD28 stimulated CD4 T cells from lymph nodes of mutants show marked decrease in Ifng (interferon-gamma) production compared to controls; in presence of Il-12, Ifng production is reduced as well

decreased T helper 1 cell number
- number of Ifng producing cells (Th1) decreases while Th2 cells producing Il-4 and Il-5 increase in number

impaired natural killer cell mediated cytotoxicity
- NK cells from mutants are impaired in ability to lyse YAC-1 cells compared to wild-type

increased natural killer cell mediated cytotoxicity
- NK cells from mutants treated with poly(I:C) for activation lyse tumor cell targets equivalently to wild-type NK cells

increased susceptibility to parasitic infection
- mutants on C57BL/6 background produce less Ifng in response to L. major infection and fail to cure infection, similar to BALB/c (susceptible) controls, while C57BL/6 (resistant) controls cure infection

increased T-helper 2 cell number
- number of Ifng producing cells (Th1) decreases while Th2 cells producing Il-4 and Il-5 increase in number

respiratory system inflammation
- homozygotes show peribronchial and perivenular infiltration with eosinophils and lymphocytes compared to wild-type littermates

respiratory system phenotype

abnormal respiratory system morphology
- mice show an increase in thickness of subbasement collagen layer of the airways, with an increased numbers of bronchial myofibroblast

increased airway responsiveness
- 4-5 week old homozygous mice exhibit airway hyperresponsiveness (AHR) to methacholine challenge, in the absence of prior immunologic sensitization; mice are more responsive without allergen challenge than wild-type mice following antigen challenge

respiratory system inflammation
- homozygotes show peribronchial and perivenular infiltration with eosinophils and lymphocytes compared to wild-type littermates

homeostasis/metabolism phenotype

abnormal cytokine level
- increased amount of TGFb is found in bronchial alveolar lavage (BAL) fluid compared to wild-type

abnormal interleukin level
- increased amounts of Il-4 and Il-13 are found in BAL fluid; Il-5 levels are high in mutants and do not increase with allergen challenge as wild-type levels do

abnormal tumor necrosis factor level
- increased amount of TNFa is found in bronchial alveolar lavage (BAL) fluid compared to wild-type

Genotype: Tbx21^tm1Glm/Tbx21⁺
involves: 129S6/SvEvTac * C57BL/6

hematopoietic system phenotype

abnormal NK cell physiology
- splenic NK cells from mutants produce less Ifng in response to Il-12 or Il-18 than NK cells from wild-type

decreased T helper 1 cell number
- only 42% of CD4 T cells produce high levels of Ifng compared to wild-type

respiratory system phenotype

abnormal respiratory system morphology
- mice show an increase in thickness of subbasement collagen layer of the airways, with an increased numbers of bronchial myofibroblast

increased airway responsiveness
- 4-5 week old homozygous mice exhibit airway hyperresponsiveness (AHR) to methacholine challenge, in the absence of prior immunologic sensitization; mice are more responsive without allergen challenge than wild-type mice following antigen challenge

homeostasis/metabolism phenotype

abnormal cytokine level
- increased amount of TGFb is found in bronchial alveolar lavage (BAL) fluid compared to wild-type

abnormal interleukin level
- increased amounts of Il-4 and Il-13 are found in BAL fluid; Il-5 levels are high in mutants and do not increase with allergen challenge as wild-type levels do

abnormal tumor necrosis factor level
- increased amount of TNFa is found in bronchial alveolar lavage (BAL) fluid compared to wild-type

immune system phenotype

abnormal cytokine level
- increased amount of TGFb is found in bronchial alveolar lavage (BAL) fluid compared to wild-type

abnormal interleukin level
- increased amounts of Il-4 and Il-13 are found in BAL fluid; Il-5 levels are high in mutants and do not increase with allergen challenge as wild-type levels do

abnormal NK cell physiology
- splenic NK cells from mutants produce less Ifng in response to Il-12 or Il-18 than NK cells from wild-type

abnormal tumor necrosis factor level
- increased amount of TNFa is found in bronchial alveolar lavage (BAL) fluid compared to wild-type

decreased T helper 1 cell number
- only 42% of CD4 T cells produce high levels of Ifng compared to wild-type

Genotype: Tbx21^tm1Glm/Tbx21^tm1Glm
B6.129S6-Tbx21

hematopoietic system phenotype

abnormal CD4-positive T cell differentiation
- mutant polarized Th17 CD4⁺ T cells fail to convert to the Th1-like state in the presence of IL-12
- wild-type CD4⁺ T cells polarized under Th17 conditions can be converted to a Th1-like cells (i.e. they express IFN-gamma) by culturing with IL-12

immune system phenotype

abnormal CD4-positive T cell differentiation
- mutant polarized Th17 CD4⁺ T cells fail to convert to the Th1-like state in the presence of IL-12
- wild-type CD4⁺ T cells polarized under Th17 conditions can be converted to a Th1-like cells (i.e. they express IFN-gamma) by culturing with IL-12

Genotype: Tbx21^tm1Glm/Tbx21^tm1Glm
involves: 129S6/SvEvTac

cellular phenotype

abnormal leukocyte migration
- Th1 and Tc1 show a modest decrease in migration to CXCL10

digestive/alimentary phenotype

increased susceptibility to induced colitis
- DSS-treated mice develop more extensive and severe inflammatory infiltrate, edema, extensive ulceration, and crypt loss compared with similarly treated wild-type mice

hematopoietic system phenotype

abnormal leukocyte migration
- Th1 and Tc1 show a modest decrease in migration to CXCL10

decreased CD4-positive, alpha beta T cell number

decreased memory T cell number
- CD4 positive

homeostasis/metabolism phenotype

abnormal cytokine level
- T cells from mice immunized with myelin oligodendrocyte glycoprotein (MOG) peptide show more interferon gamma (Ifng) and Ifng-secreting cells than wild-type ; numbers of IL-17a producing cells as well as IL-17a levels are higher than in wild-type

immune system phenotype

abnormal cytokine level
- T cells from mice immunized with myelin oligodendrocyte glycoprotein (MOG) peptide show more interferon gamma (Ifng) and Ifng-secreting cells than wild-type ; numbers of IL-17a producing cells as well as IL-17a levels are higher than in wild-type

abnormal leukocyte migration
- Th1 and Tc1 show a modest decrease in migration to CXCL10

decreased CD4-positive, alpha beta T cell number

decreased memory T cell number
- CD4 positive

increased interleukin-17 secretion
- when CD8+ T cells are cultured in Th17-polarizing conditions 2-3 fold more IL17 producing cells are produced

increased susceptibility to induced colitis
- DSS-treated mice develop more extensive and severe inflammatory infiltrate, edema, extensive ulceration, and crypt loss compared with similarly treated wild-type mice

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

Genotype: Tbx21^tm1Glm/Tbx21^tm1Glm
C.129S6-Tbx21/J

hematopoietic system phenotype

abnormal CD4-positive, alpha-beta T cell physiology
- however, recall responses of in vivo primed splenocytes from mutants 10 days after immunization are comparable to wild-type as significant proliferation in response to PLP peptide is observed ex vivo
- primed splenocytes from deficient animals produce less interferon-gamma (Ifng) than wild-type cells, but produce much increased levels of Il-10 throughout the course of the disease compared to wild-type

nervous system phenotype

CNS inflammation
- CNS of mutants show less infiltration of leukocytes into the spinal cord at 5 days after EAE onset (15 days); very little CD4+ T cell infiltration is seen compared to wild-type spinal cords

immune system phenotype

abnormal CD4-positive, alpha-beta T cell physiology
- however, recall responses of in vivo primed splenocytes from mutants 10 days after immunization are comparable to wild-type as significant proliferation in response to PLP peptide is observed ex vivo
- primed splenocytes from deficient animals produce less interferon-gamma (Ifng) than wild-type cells, but produce much increased levels of Il-10 throughout the course of the disease compared to wild-type

abnormal cytokine secretion
- wild-type mice show presence of Ifng in the spinal cord after disease development, while mutants show no Ifng but significant 1l-10 production

CNS inflammation
- CNS of mutants show less infiltration of leukocytes into the spinal cord at 5 days after EAE onset (15 days); very little CD4+ T cell infiltration is seen compared to wild-type spinal cords

decreased susceptibility to experimental autoimmune encephalomyelitis
- mutants have a very mild clinical course of disease whereas wild-type show an earlier onset and develop a higher disease grade (2.5 vs 1.25)
- Tbx21-deficient mice show a lower incidence of EAE over a period of 40 days vs wild-type controls
- upon adoptive transfer of wild-type PLP-specific T cells, mutants show decreased EAE severity compared to wild-type
- when immunized with PLP (proteolipid protein) peptide 180-199, mutants are resistant to development of clinical experimental autoimmune encephalitis (EAE) disease while wild-type littermates develop a more severe form of disease

References

Finotto S; Neurath MF; Glickman JN; Qin S; Lehr HA; Green FH; Ackerman K; Haley K; Galle PR; Szabo SJ; Drazen JM; De Sanctis GT; Glimcher LH. 2002. Development of spontaneous airway changes consistent with human asthma in mice lacking T-bet. Science 295(5553):336-8PubMed: 11786643 MGI: J:73832

Additional References

Szabo SJ; Sullivan BM; Stemmann C; Satoskar AR; Sleckman BP; Glimcher LH. 2002. Distinct effects of T-bet in TH1 lineage commitment and IFN-gamma production in CD4 and CD8 T cells. Science 295(5553):338-42PubMed: 11786644 MGI: J:73833

Additional - Tbx21^tm1Glm related

Technical Support

Contact Technical Support

Genotyping Protocols
- Standard PCR: Tbx21^tm1Glm
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice are bred as homozygotes. Coat color expected from breeding is Albino.
- Additional Breeding and Husbandry Support
Citation
When using the C.129S6-Tbx21^tm1Glm/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #004432 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	Genotype	Price
	Homozygous for Tbx21<tm1Glm>, 1 pair minimum

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.

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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

Tbx21tm1Glm

Allele Symbol: Tbx21tm1Glm

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 Genotype

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

Genotype: Tbx21tm1Glm related

Mammalian Phenotype Terms by Genotype

Genotype: Tbx21tm1Glm/Tbx21tm1Glminvolves: 129S6/SvEvTac * C57BL/6

hematopoietic system phenotype

immune system phenotype

respiratory system phenotype

homeostasis/metabolism phenotype

Genotype: Tbx21tm1Glm/Tbx21+involves: 129S6/SvEvTac * C57BL/6

hematopoietic system phenotype

respiratory system phenotype

homeostasis/metabolism phenotype

immune system phenotype

Genotype: Tbx21tm1Glm/Tbx21tm1GlmB6.129S6-Tbx21

hematopoietic system phenotype

immune system phenotype

Genotype: Tbx21tm1Glm/Tbx21tm1Glminvolves: 129S6/SvEvTac

cellular phenotype

digestive/alimentary phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

Genotype: Tbx21tm1Glm/Tbx21tm1GlmC.129S6-Tbx21/J

hematopoietic system phenotype

nervous system phenotype

immune system phenotype

References

Additional References

Additional - Tbx21tm1Glm 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

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

Tbx21^tm1Glm

Allele Symbol: Tbx21^tm1Glm

Genotype: Tbx21^tm1Glm related

Genotype: Tbx21^tm1Glm/Tbx21^tm1Glm
involves: 129S6/SvEvTac * C57BL/6

Genotype: Tbx21^tm1Glm/Tbx21⁺
involves: 129S6/SvEvTac * C57BL/6

Genotype: Tbx21^tm1Glm/Tbx21^tm1Glm
B6.129S6-Tbx21

Genotype: Tbx21^tm1Glm/Tbx21^tm1Glm
involves: 129S6/SvEvTac

Genotype: Tbx21^tm1Glm/Tbx21^tm1Glm
C.129S6-Tbx21/J

Additional - Tbx21^tm1Glm related