Mice homozygous for the Rag1tm1Mom mutation produce no mature T cells or B cells. Their phenotype can be described as a "non-leaky" immune deficiency.
Lisa M. Coussens, Oregon Health and Science University
Mice homozygous for the Rag1tm1Mom mutation produce no mature T cells or B cells. Whereas Prkdcscid homozygotes produce some B cells and IgM (i.e., are "leaky"), Rag1tm1Mom homozygotes lack all mature lymphocytes (i.e., are "non-leaky"). Rag1 null mice have no CD3+ or T cell receptor (TCR) alpha-beta positive cells. The thymus of the mutant mice contains 15 to 130 times fewer cells than heterozygous or wild-type siblings. The thymocytes are CD8-CD4- and most are IL2 receptor-positive. Neither the spleen nor the bone marrow contain any IgM or IgD staining cells, indicating an absence of mature B cells. These and other data suggest that B cell and T cell development has been arrested at an early stage. Macroscopically, the mutants are indistinguishable from heterozygotes or normal wild-type siblings.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype of these FVB/NJ-congenic mice could vary from that originally described on a B6.129S7 congenic background. We may modify the strain description if necessary as published results become available.
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 129S7/SvEvBrd-Hprt+-derived AB1 embryonic stem cell line was used and mice are maintained on a congenic C57BL/6J background as Stock No. 002216. Dr. Lisa Coussens (Oregon Health and Science University) obtained some of these mice and further backcrossed them to FVB/NJ mice (Stock No. 001800)
for at least 10 generations before sending mice back to The Jackson Laboratory. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize FVB/NJ oocytes.
|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
This Rag1tm1Mom strain is maintained by mating homozygous siblings. This strain should be housed under pathogen free conditions similar to Prkdcscid/Prkdcscid mice or any other immunodeficient strain. Only homozygous mice may be ordered.
When using the Rag1 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #032562 in your Materials and Methods section.
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