B6.129-Rag1^tm1Mom Fcgrt^tm1Dcr/DcrJ

Stock number: 017700
Product name: Rag1- mFcRn-
Research areas: Cancer Research, Cell Biology Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Neurobiology Research, Research Tools

Description

Rag1-/- FcRn-/- mice are immunodeficient and therefore suitable for xenograft assays. They may be useful in testing therapeutic compounds and their involvement in the FcRn pathway or as a control for immunocompromised humanized FcRn transgenics.

Detailed description

The neonatal Fc receptor, encoded by the Fcgrt gene, is a MHC class I like molecule. One of its functions is to protect IgG and albumin from degradation, and to mediate the transport of IgG across epithelial cells. Further, it plays a role in antigen presentation by professional antigen presenting cells. It has been demonstrated that FcRn is critical for the materno-fetal transport and intestinal uptake of IgG.

Mice that are homozygous for the FcRn α-chain and Rag1 knockout mutations are viable and fertile. Homozygotes exhibit a low plasma albumin concentration due to the lack of murine FcRn (see strain description Stock No. 003982) and lack mature B- and T-cells caused by the Rag1 knockout (see strain description Stock No. 002216). It is possible to perform xenograft studies in these mice and to study the involvement of the FcRn pathway in response to administered compounds, especially when compared with the humanized Rag1-/- FcRn-/- hFcRn transgenic mice (see Stock No. 016919), for which these mice serve as a control.

Development

These Rag1-/- mFcRn-/- mice were produced by crossing STOCK No. 003982 mice with STOCK No. 002216. The double mutant mice were backcrossed to C57BL/6 for 10 generations.

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: Fcgrt^tm1Dcr
Name: targeted mutation 1, Derry C Roopenian
MGI accession ID: MGI:3511510
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Fcgrt
Marker name: Fc receptor, IgG, alpha chain transporter
Chromosome: 7
Strain of origin: 129X1/SvJ
Molecular note: Sequence from exon 1 and part of exon2 was replaced with a PGK-neo cassette. Quantitative PCR of liver cDNA indicated the absence of mRNA. Western blot analysis of neonatal intestinal extracts failed to reveal protein product.