NOD.Cg-Rag1^tm1Mom Prf1^tm1Sdz/SzJ

Stock number: 004848
Product name: NOD/LtSz-Rag1nullPfpnull
Research areas: Apoptosis Research, Cancer Research, Developmental Biology Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools

Description

These double knock-out mutant mice have no mature T or B lymphocytes, no detectable NK cell cytotoxic activity, and lack serum immunoglobulin. They also develop thymic lymphomas.

Detailed description

Mice that are homozygous for both targeted mutations are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities when housed under specific pathogen free conditions. These double homozygote mutant mice have no mature T or B lymphocytes, no detectable NK cell cytotoxic activity, and lack serum immunoglobulin. The number of nucleated spleen cells is significantly reduced in double mutant mice, when compared to the single homozygote, NOD.129S7(B6)-Rag1^tm1Mom/J (Stock No. 003729). Although an increased number of DX5⁺CD122⁺ NK cells are found in the spleens of double mutants, these NK cells have impaired cytotoxic activity. The disruption of Prf1 ablates NK cell cytotoxic activity resulting in increased engraftment levels over that observed with Stock No. 003729. All mutant mice develop thymic lymphomas. This double mutant mouse strain may be useful in studies involving engraftment of human hematolymphoid cells.

Development

Please see strain entries Stock No. 002407 and Stock No. 003729 for details regarding the construction of each mutant allele. This strain was produced by crossing female NOD.129S7(B6)-Rag1^tm1Mom/J (Stock No. 003729) to male C57BL/6-Prf1^tm1Sdz (Stock No. 002407). Resulting female progeny heterozygous for both mutant alleles were crossed to male NOD.129S7(B6)-Rag1^tm1Mom/J (Stock No. 003729). Mice homozygous for the Rag1 mutant allele and heterozygous for the Prf1 allele were crossed to NOD.129S7(B6)-Rag1^tm1Mom/J (Stock No. 003729) mice for 10 generations, and then intercrossed to produce double homozygotes.

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-Hprt1⁺
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.

Allele

Symbol: Prf1^tm1Sdz
Name: targeted mutation 1, Sandoz Pharmaceuticals
MGI accession ID: MGI:1857235
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Prf1
Marker name: perforin 1 (pore forming protein)
Chromosome: 10
Strain of origin: C57BL/6
Molecular note: A neomycin selection cassette was inserted into exon 3. RT-PCR analysis on RNA derived from homozygous mice demonstrated that an abnormal transcript was produced from this allele. However, immunocytochemistry experiments on activated spleen cells derived from homozygous mice confirmed that no detectable protein was made from this allele.