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.Read More +
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 Tcratm1Mjo 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).
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 Tcratm1Mjo 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 Tcrtm1Mjo 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.
|Allele Name||accelerated autoimmunity and lymphoproliferation|
|Allele Synonym(s)||Is(XOfd1-Mid1;Y)1Mp; Tp(X;Y)1Ekw|
|Gene Symbol and Name||Yaa, accelerated autoimmunity and lymphoproliferation transposition|
|Strain of Origin||SB/Le|
|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.|
|Allele Name||targeted mutation 1, Michael J Owen|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Calpha-; Tcratm1Phi; TCRalpha; Tcralpha-; TCRalpha KO; TCRalphae-|
|Gene Symbol and Name||Tcra, T cell receptor alpha chain|
|Strain of Origin||129P2/OlaHsd|
|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