Overview

This faculty strain has been discontinued but is available as Stock No. 007878.

This BXSB congenic strain lacks alpha/beta T cells and thus the homozygous null males do not develop the Yaa-induced lupus-like autoimmune disease. Mice from this strain are valuable for adoptive transfer experiments that study the role of T cells in systemic autoimmunity and lupus.

Genetic overview

Genetic Background	Generation
000740 BXSB/MpJ

Yaa

Allele Type	Gene Symbol	Gene Name
Spontaneous	Yaa	accelerated autoimmunity and lymphoproliferation transposition

Tcra^tm1Mjo

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Tcra	T cell receptor alpha chain

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Research Applications

Immunology, Inflammation and Autoimmunity Research
Research Tools
Hematological Research

View All Research Applications

Details

Detailed Description

Male mice on the BXSB recombinant inbred genetic background (see Stock No. 000740) develop spontaneous autoimmune disease closely resembling the human disease systemic lupus erythematosus (SLE), including moderate lymph node and spleen enlargement, hemolytic anemia, hypergammaglobulinemia, and immune complex glomerulonephritis. Homozygotes for the Tcra^tm1Mjo null allele lack alpha/beta T cells, which are essential for the development of the lupus-like autoimmune disease of Yaa-bearing males on the BXSB/MpJ background. Lacking alpha/beta T cells, these homozygotes do not develop anti-chromatin autoantibodies or hypergammaglobulinemia, do not develop glomerulonephritis, do not have the expanded Mac1⁺ MHC class II negative monocytosis, which is found in BXSB/MpJ males, but instead were found to survive 300 days essentially disease-free. Transfer of alpha/beta T cells from adult BXSB mice into these TCR alpha/beta null hosts conferred disease to the host even when the donor was female and therefore lacking the Yaa translocation (Lawson et al., 2001).

Development

A targeting vector, using sequence isolated from a genomic library of embryonic BALB/c DNA, was designed to disrupt the first exon of the T cell receptor alpha constant region with a neomycin cassette. This construct was electroporated into 129P2/OlaHsd-derived GK129 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric founders were bred to BALB/c to generate mutant mice. These mice were then crossed with C57BL/6 inbred mice in the laboratory of Dr. Michael J. Owen (Imperial Cancer Research Fund). Mice were then sent to Dr. Argyrios N. Theofilopoulos (The Scripps Research Institute) and the Tcra^tm1Mjo allele subsequently backcrossed onto a subline of the BXSB recombinant inbred strain (BXSB/MpScr). Upon arrival at The Jackson Laboratory, homozygotes were intercrossed for rederivation and males at generation N8F45 were transferred to the laboratory of Dr. Derry Roopenian where it was observed that the satin mutation was in the imported strain. A homozygous male was bred to a BXSB/MpJ female (stock number 000740) and the Tcr^tm1Mjo allele was backcrossed onto BXSB/MpJ for 6 more generations reaching N14 before intercrossing to homozygosity. During the backcrossing the satin mutation was bred out of this strain. In 2017 this strain reached generation N14F24. A similar strain is cryopreserved, see stock number 007848.

Control Suggestions

000740 BXSB/MpJ

Additional Information

Considerations for Choosing Controls

Selected References

Lawson BR; Koundouris SI; Barnhouse M; Dummer W; Baccala R; Kono DH; Theofilopoulos AN. 2001. The role of alpha beta+ T cells and homeostatic T cell proliferation in Y-chromosome-associated murine lupus. J Immunol 167(4):2354-60PubMed: 11490025 MGI: J:120153

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Genetics

Yaa

Allele Symbol: Yaa

Allele Name	accelerated autoimmunity and lymphoproliferation
Allele Type	Spontaneous
Allele Synonym(s)	Is(XOfd1-Mid1;Y)1Mp; Tp(X;Y)1Ekw
Gene Symbol and Name	Yaa, accelerated autoimmunity and lymphoproliferation transposition
Gene Synonym(s)
Strain of Origin	SB/Le
Chromosome	Y
Molecular Note	An approximately 4 MB region of the X chromosome that includes at least 13 known genes (spanning from Ofd1 to Mid1) was translocated to the Y chromosome adjacent to the pseudoautosomal region. Increased RNA expression of Msl3, Tlr7, Tmsb4x and Rab9 was detected in follicular B cells.

Tcra^tm1Mjo

Allele Symbol: Tcra^tm1Mjo

Allele Name	targeted mutation 1, Michael J Owen
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Calpha-; Tcra^tm1Phi; TCRalpha; Tcralpha-; TCRalpha KO; TCRalphae^-
Gene Symbol and Name	Tcra, T cell receptor alpha chain
Gene Synonym(s)
Strain of Origin	129P2/OlaHsd
Chromosome	14
Molecular Note	The Tcra-C element C1 was disrupted by the insertion of a neomycin selection cassette.
Mutations Made By	Michael Owen, Imperial Cancer Research Fund

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Genotype: Tcra^tm1Mjo related

Immunology, Inflammation and Autoimmunity Research
- T Cell Receptor Signaling Defects
- CD Antigens, Antigen Receptors, and Histocompatibility Markers
- Immunodeficiency
- Inflammation
Research Tools
- Cancer Research
  - specific T cell deficiency
Hematological Research
- Immunological Defects

Genotype: Yaa related

Immunology, Inflammation and Autoimmunity Research
- Autoimmunity
  - lupus erythematosus

Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - T cell deficiency
- Autoimmunity

Mammalian Phenotype Terms by Genotype

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

Genotype: Tcra^tm1Mjo/Tcra^tm1Mjo X/Yaa
BXSB.129P2(Cg)-Tcra/Theo

mammalian phenotype

immune system phenotype
- Normal - due to the absense of alpha/beta T cells these Yaa-bearing males do not develop hypergammaglobulinemia, anti-chromatin auto-antibodies, enlarged lymph nodes or spleen, hemolytic anemia, immune complex glomerulonephritis, monocytosis, or the lupus-like autoimmune disease that normally causes premature death in Yaa-bearing males on the BXSB background, but instead these males are reported to live beyond 300 days

References

Lawson BR; Koundouris SI; Barnhouse M; Dummer W; Baccala R; Kono DH; Theofilopoulos AN. 2001. The role of alpha beta+ T cells and homeostatic T cell proliferation in Y-chromosome-associated murine lupus. J Immunol 167(4):2354-60PubMed: 11490025 MGI: J:120153

Additional - Tcra^tm1Mjo related

Additional - Yaa related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Genotyping resources and troubleshooting
Mating System
- Homozygote x Homozygote

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

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Genetic overview

Research Applications

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Yaa

Allele Symbol: Yaa

Tcratm1Mjo

Allele Symbol: Tcratm1Mjo

Disease Terms

Research Areas By Phenotype

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

Genotype: Tcratm1Mjo related

Genotype: Yaa related

Mammalian Phenotype Terms by Genotype

Genotype: Tcratm1Mjo/Tcratm1Mjo X/YaaBXSB.129P2(Cg)-Tcra/Theo

mammalian phenotype

References

Additional - Tcratm1Mjo related

Additional - Yaa related

Genotyping Protocols

Mating System

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

Tcra^tm1Mjo

Allele Symbol: Tcra^tm1Mjo

Genotype: Tcra^tm1Mjo related

Genotype: Tcra^tm1Mjo/Tcra^tm1Mjo X/Yaa
BXSB.129P2(Cg)-Tcra/Theo

Additional - Tcra^tm1Mjo related