Overview

Also Known As:T-bet^-

T cells from the lymph nodes of T-bet^- mice lack T-box transcription factor TBX21, and may be useful in studies of acute and chronic asthma and chronic intestinal inflammation.

Donating Investigator

Dr. Laurie H. Glimcher, Dana Farber Cancer Institute

Genetic overview

Genetic Background	Generation
	N10F9 (2021-09-05 00:00:00)

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:

$236.78 Domestic price for female 4-week

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Details

Detailed Description

Mice that are homozygous for the targeted mutation are viable, fertile and normal in size. No gene product (mRNA or protein) is detected in isolated lymph node T cells by Northern or Western blot analysis. The IFN-γ cytokine induced by CD4 T or NK cells from homozygotes is markedly reduced. CD4 T cells do not produce the TH1-type cytokine interferon gamma but secrete elevated levels of TH2-type cytokines in response to in vitro T cell receptor (TCR) cross-linking and in vivo protein antigen immunization. Additionally, mice homozygous for the targeted mutation on this genetic background are susceptible to Leishmania major infections. Without induced sensitization or challenge, female homozygotes display hyper-responsiveness (AHR) with resulting airway remodeling similar to characteristics of asthma. Histological analysis of lung tissue 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 TGFB1 (TGF-beta 1), TNF (TNF-alpha), IL4 and IL13. Mice heterozygous for the targeted mutation display an intermediate phenotype.

Development

A targeting vector was designed to replace exon 1 of the T-box 21 (Tbx21) gene with a neomycin resistance (neo) cassette. The construct was electroporated into 129S6/SvEvTac-derived TC-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric males were bred to C57BL/6 females. These mice were backcrossed to C57BL/6 mice for at least 8 generations. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

Control Suggestions

000664 C57BL/6J

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

View All References

Genetics

Tbx21^tm1Glm

Allele Symbol: Tbx21^tm1Glm

Allele Name	targeted mutation 1, Laurie H Glimcher
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	T-bet^-; Tbx21-
Gene Symbol and Name	Tbx21, T-box 21
Gene Synonym(s)
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 Phenotype

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

Genotype: Tbx21^tm1Glm related

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

Immunology, Inflammation and Autoimmunity Research
- Inflammation
  - Inflammatory bowel disease

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

homeostasis/metabolism phenotype

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

abnormal cytokine level
- increased amount of TGFb 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 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 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

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

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

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

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

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

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

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

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

hematopoietic system phenotype

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

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

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

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

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

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

respiratory system phenotype

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

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

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

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

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

hematopoietic system phenotype

abnormal CD4-positive, alpha-beta T cell physiology
- 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
- 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

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

decreased susceptibility to experimental autoimmune encephalomyelitis
- Tbx21-deficient mice show a lower incidence of EAE over a period of 40 days vs wild-type controls
- 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
- upon adoptive transfer of wild-type PLP-specific T cells, mutants show decreased EAE severity compared to wild-type
- 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)

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

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

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

cellular phenotype

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

immune system 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

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

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

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

decreased CD4-positive, alpha beta T cell number

decreased memory T cell number
- CD4 positive

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

decreased CD4-positive, alpha beta T cell number

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

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

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

respiratory system phenotype

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

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

hematopoietic system phenotype

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

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

homeostasis/metabolism phenotype

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

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

immune system phenotype

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

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

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

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

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

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

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
- Separated MCA:Tbx21 MCA SEP
- Standard PCR:Tbx21 MCA SEP
- Genotyping resources and troubleshooting
Dietary Information
- LabDiet® 5K52 formulation (6% fat)
Breeding Considerations

The resulting chimeric animals were crossed to C57BL/6 mice, and then backcrossed to C57BL/6 for 8 generations. The strain is maintained as a homozygote. Expected coat color is black non-agouti.
- Additional Breeding and Husbandry Support
Mating System
- Homozygote x Homozygote
Citation
When using the T-bet^- mouse strain in a publication, please cite the originating article(s) and include JAX stock #004648 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX11 (Maximum)

Pricing & Availability

Available

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
> >	Heterozygous for Tbx21<tm1Glm>

Related Products and Services

Frozen Mouse Embryo	B6.129S6-Tbx21<tm1Glm>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	B6.129S6-Tbx21<tm1Glm>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	B6.129S6-Tbx21<tm1Glm>/J Frozen Embryos	$3373.50
Frozen Mouse Embryo	B6.129S6-Tbx21<tm1Glm>/J Frozen Embryos	$3373.50

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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

Also Known As:T-bet-

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 Phenotype

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

homeostasis/metabolism phenotype

immune system phenotype

hematopoietic system phenotype

respiratory system phenotype

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

nervous system phenotype

hematopoietic system phenotype

immune system phenotype

Genotype: Tbx21tm1Glm/Tbx21tm1Glminvolves: 129S6/SvEvTac

cellular phenotype

immune system phenotype

digestive/alimentary phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

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

respiratory system phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

Genotype: Tbx21tm1Glm/Tbx21tm1GlmB6.129S6-Tbx21

hematopoietic system phenotype

immune system phenotype

References

Additional References

Additional - Tbx21tm1Glm related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Citation

Animal Health Reports

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Also Known As:T-bet^-

Tbx21^tm1Glm

Allele Symbol: Tbx21^tm1Glm

Genotype: Tbx21^tm1Glm related

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

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

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

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

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

Additional - Tbx21^tm1Glm related