Strain Name:

B6.129S-Themistm1Gasc/J

Stock Number:

010919

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Themis-/- mice contain a mutation designed to disrupt gene function of endogenous mouse Themis. These mice may be useful for studying positive selection of thymocytes and early events in the TCR signaling cascade.

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
 
Donating Investigator Nicholas Gascoigne,   The Scripps Research Institute

Description
These Themis-/- mice contain a mutation designed to disrupt the gene function of endogenous mouse Themis. Homozygous mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Thymocytes from these mice show defective positive selection resulting in fewer mature single positive thymocytes, and show impaired negative selection. This may be due to defective T cell antigen receptor (TCR) signal transduction and/or a so-far undefined signaling or metabolic defect. The defect in positive selection results in altered thymus structure, with the medulla being smaller and more fragmented than wild-type medulla. A greater percentage of Themis-/- T cells have CD4+CD25+Foxp3+ regulatory and CD62LloCD44hi memory phenotypes than do wild-type T cells. These mice may be useful for studying positive selection of thymocytes and early events in the TCR signaling cascade.

Development
A targeting vector was designed to replace exon 1 of the mouse thymocyte-expressed molecule involved in selection (Themis) locus with a PGK neomycin-resistance cassette. This construct was electroporated into 129S/SvEv-derived CMTI-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into a recipient blastocysts and the resulting chimeric males were bred to C57BL/6J females to establish a colony of Themis deficient (Themis-/-) mice. These mutant mice were backcrossed at least 10 generations to C57BL/6J mice prior to arrival at The Jackson Laboratory. Upon arrival, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

Control Information

  Control
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Themistm1Gasc/Themistm1Gasc

        B6.129S-Themistm1Gasc
  • immune system phenotype
  • abnormal memory T cell morphology
    • the relative frequency of memory T cells in the periphery is increased, probably indicating an expansion of a small population of nażve T cells   (MGI Ref ID J:151074)
  • abnormal positive T cell selection
    • TCR and CD69 expression levels suggest positive selection is mostly blocked at its earliest stage during which CD8 downregulation is initiated   (MGI Ref ID J:151074)
    • bone marrow chimera experiments demonstrate that positive selection is intrinsic to the thymocytes   (MGI Ref ID J:151074)
  • abnormal regulatory T cell morphology
    • FoxP3+ regulatory T cells are increased in frequency (21%) but only have half the absolute numbers as wild-type controls   (MGI Ref ID J:151074)
  • abnormal thymus medulla morphology
    • thymus medulla is smaller and more fragmented than controls   (MGI Ref ID J:151074)
  • decreased CD4-positive, alpha beta T cell number
    • CD4+ single-positive thymocyte numbers are reduced by about half   (MGI Ref ID J:151074)
    • CD4+ T cells in the periphery are reduced about 10-fold   (MGI Ref ID J:151074)
  • decreased CD8-positive, alpha-beta T cell number
    • CD8+ single-positive thymocyte numbers are reduced by about half   (MGI Ref ID J:151074)
    • CD8+ T cells in the periphery are reduced about 5-fold   (MGI Ref ID J:151074)
  • decreased T cell proliferation
    • T cell proliferation in response to anti-CD3 stimulation is very poor compared to controls   (MGI Ref ID J:151074)
  • decreased thymocyte number
    • the number of thymocytes with an intermediate expression of CD69 and TCR is decreased in these mice   (MGI Ref ID J:151074)
    • there is considerable depletion of TCRhiCD69hi thymocytes   (MGI Ref ID J:151074)
    • these TCRhiCD69hi thymocytes are double-positive or CD8-single positive compared to wild-type controls where this population is almost exclusively single-positive   (MGI Ref ID J:151074)
  • increased double-positive T cell number
    • the proportion and number of double-positive thymocytes is slightly but significantly greater   (MGI Ref ID J:151074)
  • hematopoietic system phenotype
  • abnormal memory T cell morphology
    • the relative frequency of memory T cells in the periphery is increased, probably indicating an expansion of a small population of nażve T cells   (MGI Ref ID J:151074)
  • abnormal positive T cell selection
    • TCR and CD69 expression levels suggest positive selection is mostly blocked at its earliest stage during which CD8 downregulation is initiated   (MGI Ref ID J:151074)
    • bone marrow chimera experiments demonstrate that positive selection is intrinsic to the thymocytes   (MGI Ref ID J:151074)
  • abnormal regulatory T cell morphology
    • FoxP3+ regulatory T cells are increased in frequency (21%) but only have half the absolute numbers as wild-type controls   (MGI Ref ID J:151074)
  • abnormal thymus medulla morphology
    • thymus medulla is smaller and more fragmented than controls   (MGI Ref ID J:151074)
  • decreased CD4-positive, alpha beta T cell number
    • CD4+ single-positive thymocyte numbers are reduced by about half   (MGI Ref ID J:151074)
    • CD4+ T cells in the periphery are reduced about 10-fold   (MGI Ref ID J:151074)
  • decreased CD8-positive, alpha-beta T cell number
    • CD8+ single-positive thymocyte numbers are reduced by about half   (MGI Ref ID J:151074)
    • CD8+ T cells in the periphery are reduced about 5-fold   (MGI Ref ID J:151074)
  • decreased T cell proliferation
    • T cell proliferation in response to anti-CD3 stimulation is very poor compared to controls   (MGI Ref ID J:151074)
  • decreased thymocyte number
    • the number of thymocytes with an intermediate expression of CD69 and TCR is decreased in these mice   (MGI Ref ID J:151074)
    • there is considerable depletion of TCRhiCD69hi thymocytes   (MGI Ref ID J:151074)
    • these TCRhiCD69hi thymocytes are double-positive or CD8-single positive compared to wild-type controls where this population is almost exclusively single-positive   (MGI Ref ID J:151074)
  • increased double-positive T cell number
    • the proportion and number of double-positive thymocytes is slightly but significantly greater   (MGI Ref ID J:151074)
  • endocrine/exocrine gland phenotype
  • abnormal thymus medulla morphology
    • thymus medulla is smaller and more fragmented than controls   (MGI Ref ID J:151074)
  • decreased thymocyte number
    • the number of thymocytes with an intermediate expression of CD69 and TCR is decreased in these mice   (MGI Ref ID J:151074)
    • there is considerable depletion of TCRhiCD69hi thymocytes   (MGI Ref ID J:151074)
    • these TCRhiCD69hi thymocytes are double-positive or CD8-single positive compared to wild-type controls where this population is almost exclusively single-positive   (MGI Ref ID J:151074)
View Research Applications

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

Immunology, Inflammation and Autoimmunity Research
Immunodeficiency
      T cell deficiency
T Cell Receptor Signaling Defects

Internal/Organ Research
Thymus Defects

Research Tools
Immunology, Inflammation and Autoimmunity Research
      specific T cell deficiency

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Themistm1Gasc
Allele Name targeted mutation 1, Nicholas R J Gascoigne
Allele Type Targeted (Null/Knockout)
Common Name(s) Themis-;
Mutation Made By Nicholas Gascoigne,   The Scripps Research Institute
Strain of Origin129S6/SvEvTac
Gene Symbol and Name Themis, thymocyte selection associated
Chromosome 10
Gene Common Name(s) BB160712; C6orf190; C6orf207; E430004N04Rik; GASP; RGD1560849; RIKEN cDNA E430004N04 gene; SPOT; TSEPA; Tsepa; bA325O24.3; bA325O24.4; expressed sequence BB160712; thymocyte selection pathway associated;
Molecular Note A neomycin cassette replaced exon 1 of the gene locus. Gene inactivation was confirmed by a lack of protein detected in immunoblot assays of homozygote thymus extract. [MGI Ref ID J:151074]

Genotyping

Genotyping Information

Genotyping Protocols

Themistm1Gasc alternative1, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Fu G; Vallee S; Rybakin V; McGuire MV; Ampudia J; Brockmeyer C; Salek M; Fallen PR; Hoerter JA; Munshi A; Huang YH; Hu J; Fox HS; Sauer K; Acuto O; Gascoigne NR. 2009. Themis controls thymocyte selection through regulation of T cell antigen receptor-mediated signaling. Nat Immunol 10(8):848-56. [PubMed: 19597499]  [MGI Ref ID J:151074]

Additional References

Themistm1Gasc related

Fu G; Casas J; Rigaud S; Rybakin V; Lambolez F; Brzostek J; Hoerter JA; Paster W; Acuto O; Cheroutre H; Sauer K; Gascoigne NR. 2013. Themis sets the signal threshold for positive and negative selection in T-cell development. Nature 504(7480):441-5. [PubMed: 24226767]  [MGI Ref ID J:207761]

Paster W; Brockmeyer C; Fu G; Simister PC; de Wet B; Martinez-Riano A; Hoerter JA; Feller SM; Wulfing C; Gascoigne NR; Acuto O. 2013. GRB2-Mediated Recruitment of THEMIS to LAT Is Essential for Thymocyte Development. J Immunol 190(7):3749-56. [PubMed: 23460737]  [MGI Ref ID J:194815]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, homozygous mice may be bred together.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2140.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2782.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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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