NOD.129S7(B6)-Rag1^tm1Mom/J

Stock number: 003729
Product name: Rag1 KO
Research areas: Cancer Research, Diabetes and Obesity Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools

Description

Mice homozygous for Rag1^tm1Mom 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.

Detailed description

Mice homozygous for the Rag1^tm1Mom mutation produce no mature T cells or B cells. Their phenotype can be described as a "non-leaky" severe combined immune deficiency. (Prkdc^scid/Prkdc^scid) mice produce some B cells and IgM. NOD.129S7(B6)-Rag1^tm1Mom/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-Prkdc^scid/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.

Development

The Rag1^tm1Mom 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

Symbol: Rag1^tm1Mom
Name: targeted mutation 1, Peter Mombaerts
MGI accession ID: MGI:1857241
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Rag1
Marker name: recombination activating gene 1
Chromosome: 2
Strain of origin: 129S7/SvEvBrd-Hprt⁺
Site of expression: expression is seen in bone marrow derived cell lines.
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.