Mice homozygous for Rag1tm1Mom produce no mature T cells or B cells. The thymus in mutant mice is severely involuted. B cell and T cell development is apparently arrested at an early stage. These characteristics qualify this strain as a useful tool for HIV-1 studies and research involving human hematolymphoid cell engraftment or NOD diabetes pathogenesis.
Dr. Leonard D. Shultz, The Jackson Laboratory
Mice homozygous for the Rag1tm1Mom mutation produce no mature T cells or B cells. Their phenotype can be described as a "non-leaky" severe combined immune deficiency. (Prkdcscid/Prkdcscid) mice produce some B cells and IgM. NOD.129S7(B6)-Rag1tm1Mom/J mice have no CD3+ or T cell receptor (TCR) alpha-beta positive cells. The thymus of the mutant mice is severely involuted. The thymocytes are CD8-CD4- and most are IL2 receptor positive. Neither the spleen nor bone marrow contain any IgM or IgD staining cells, indicating an absence of mature B cells. These and other data suggest that both B cell and T cell development have been arrested at an early stage. Macroscopically, the mutants are indistinguishable from heterozygotes or normal wildtype siblings. Notable differences between this strain and the NOD.CB17-Prkdcscid/J strain (Stock No. 001303) include a longer life span due to delayed onset of lymphoma development, greater radioresistance and a complete absence of serum Ig. These characteristics qualify this strain as a useful tool for HIV-1 studies and research involving human hematolymphoid cell engraftment or NOD diabetes pathogenesis.
The Rag1tm1Mom mutant strain was developed by Dr. Peter Mombaerts in the laboratory of Dr. Susumu Tonegawa at the Center for Cancer Research, Massachusetts Institute of Technology. A replacement targeting vector with the Pgk-neo marker was used. Homologous recombination of the targeting vector resulted in a 1356 bp deletion in the 5' end of the coding sequence. The 129-derived AB1 ES cell line was used.
|Allele Name||targeted mutation 1, Peter Mombaerts|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Rag-; Rag1tm1Mom; RAG-1-; Rag1-; RAG1null; Rag-1KO|
|Gene Symbol and Name||Rag1, recombination activating gene 1|
|Site of Expression||expression is seen in bone marrow derived cell lines.|
|Strain of Origin||129S7/SvEvBrd-Hprt+|
|Molecular Note||A 1356 bp genomic fragment of the Rag1 gene, encoding the nuclear localization signal and the zinc-finger motif, was replaced by a neomycin cassette. A mutant transcript expressed from this allele was detected by Northern blot in bone marrow derived cell lines from homozygous mice.|
|Mutations Made By|| |
Peter Mombaerts, Max Planck Research Unit for Neurogenetics
The original B6,129S-Rag1tm1Mom line was backcrossed to the NOD/LtSz strain background for ten generations. At the tenth generation, mice were intercrossed. They are now being maintained as homozygotes. These mice are severely immunodeficient so specific pathogen-free (SPF) conditions are recommended. Coat color expected from breeding: albino
When using the Rag1 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #003729 in your Materials and Methods section.