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. Species laboratory 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

Themis^tm1Gasc/Themis^tm1Gasc

        B6.129S-Themis^tm1Gasc

• 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 naïve 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 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 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 TCR^hiCD69^hi thymocytes   (MGI Ref ID J:151074)
  • these TCR^hiCD69^hi 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 naïve 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 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 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 TCR^hiCD69^hi thymocytes   (MGI Ref ID J:151074)
  • these TCR^hiCD69^hi 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)
• cellular phenotype
• 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)
• decreased T cell proliferation
  • T cell proliferation in response to anti-CD3 stimulation is very poor compared to controls   (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)

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 and Inflammation 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 (knock-out)
Common Name(s)		Themis-;
Mutation Made By		Nicholas Gascoigne,   The Scripps Research Institute
Strain of Origin		129S6/SvEvTac
Gene Symbol and Name		Themis, thymocyte selection associated
Chromosome		10
Gene Common Name(s)		BB160712; C6orf190; C6orf207; E430004N04Rik; GASP; 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

Themis^tm1Gasc 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

Themis^tm1Gasc related

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 & Husbandry	When maintaining a live colony, homozygous mice may be bred together.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

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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