Rag1 Fcgrt FCGRT knock-out/transgenic mice are immunodeficient and therefore applicable for xenograft studies. This humanized model may be useful in evaluating the pharmacokinetics, the pharmacodynamics and/or efficacy testing of human Fc-based molecules (e.g. human IgG, Fc-fusion proteins) or for analyzing the immunogenicity of antibodies.
Need assistance evaluating antibodies in FcRn mice? Human preclinical pharmacokinetic (PK) analysis is available. See our FcRn full service platform.
Dr. Derry Roopenian, The Jackson Laboratory
Genetic Background | Generation |
---|---|
|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Rag1 | recombination activating gene 1 |
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Fcgrt | Fc receptor, IgG, alpha chain transporter |
Allele Type |
---|
Transgenic (Inserted expressed sequence, Humanized sequence) |
Rag1 Fcgrt FCGRT mice harbor knockout alleles of the Fcgrt (formerly FcRn) and Rag1 genes and express a human FCGRT (FcRn α-chain) transgene under the CAG promoter. These mice have a normal level of serum albumin, but are deficient in mature B- and T-cells. In this model, longer half-lives are observed with mice homozygous for the human FCGRT transgene when compared to hemizygous mice, indicating that higher copy number correlates with higher expression of FcRn and provides greater protection of IgG from clearance. This model is useful for pharmacokinetic and pharmacodynamic studies of human IgG. It has been shown to be useful for screening of hIgGs in evaluations of serum half-life. Being immunodeficient, they are suitable for efficacy testing requiring xenografts. Zalevsky et. al. 2010 have shown good correlation between this mouse model and studies performed with Cynomolgus monkeys.
These Rag1-/- mFcRn-/- hFcRn Tg 276 mice were produced by crossing STOCK No. 004919 mice with STOCK No. 002216.
FcRn α-chain knockout mice expressing a human FcRn transgene (line 276) are also called FcRn-/- hFcRn (276) Tg mice, cDNA transgenic line 276, mFcRn-/- hFcRn (276) Tg [carrying one allele of the transgene] (STOCK No. 004919). The FcRn-/- hFcRn (276) Tg mice were generated in the laboratory of Derry Roopenian (The Jackson Laboratory) by crossing Fcgrttm1Dcr targeted mutant mice (backcrossed five generations to C57BL/6J) with Tg(CAG-FCGRT)276Dcr transgenic mice (coisogenic on a C57BL/6J genetic background).
To generate the FcRn α-chain knockout mice (Fcgrttm1Dcr; see also Stock No. 003982), a targeting vector was designed to replace 1588 nucleotide fragments (encoding promoter sequence 5' of the transcriptional start site, exon1, intron 2, and most of exon2) with a PGK-Neor cassette. The vector was electroporated into 129/SvJ-derived ESV/J-1182 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to C57BL/6J mice. These FcRn α-chain mutant mice were backcrossed to C57BL/6J for five generations prior to breeding with hFcRn line 276 transgenic mice.
To generate the hFcRn line 276 transgenic mice, a transgene was designed with the 0.34 kb human cytomegalovirus immediate early promoter enhancer, 1.4 kb chicken beta-actin promoter and intron 1, a cDNA sequence encoding the human FcRn α-chain, 0.73 kb rabbit beta-globin intron, and 0.35 kb SV40 polyA sequence. The donating investigator reports that this transgene was injected into C57BL/6J embryos. The resulting transgenic offspring were bred to C57BL/6J mice to establish founder line 276. These hFcRn line 276 transgenic mice were maintained on a C57BL/6J genetic background prior to breeding with mice carrying the Fcgrttm1Dcr allele.
Expressed Gene | FCGRT, Fc fragment of IgG receptor and transporter, human |
---|---|
Site of Expression |
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 |
Gene Synonym(s) | |
Site of Expression | expression is seen in bone marrow derived cell lines. |
Strain of Origin | 129S7/SvEvBrd-Hprt+ |
Chromosome | 2 |
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 |
Allele Name | targeted mutation 1, Derry C Roopenian |
---|---|
Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | FcRn- |
Gene Symbol and Name | Fcgrt, Fc receptor, IgG, alpha chain transporter |
Gene Synonym(s) | |
Strain of Origin | 129X1/SvJ |
Chromosome | 7 |
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. |
Allele Name | transgene insertion 276, Derry C Roopenian |
---|---|
Allele Type | Transgenic (Inserted expressed sequence, Humanized sequence) |
Allele Synonym(s) | hFcRn (276) Tg; Tg276 |
Gene Symbol and Name | Tg(CAG-FCGRT)276Dcr, transgene insertion 276, Derry C Roopenian |
Gene Synonym(s) | |
Promoter | ACTB, actin, beta, chicken |
Expressed Gene | FCGRT, Fc fragment of IgG receptor and transporter, human |
Strain of Origin | C57BL/6J |
Chromosome | 1 |
Molecular Note | To generate the hFcRn line 276 transgenic mice, a transgene was designed with the 0.34 kb human cytomegalovirus immediate early promoter enhancer, 1.4 kb chicken beta-actin promoter and intron 1, a cDNA sequence encoding the human FcRn alpha-chain, 0.73 kb rabbit beta-globin intron, and 0.35 kb SV40 polyA sequence. Line 276 was established. Transgene insertion occurred on Chr 1, causing a 1 bp duplication. |
When maintaining a live colony, mice homozygous for the FcRn α-chain targeted allele (Fcgrttm1Dcr), homozygous for the RAG1null allele (Rag1tm1Mom), and hemizygous or homozygous for the hFcRn (276) transgene (Tg(CAG-FCGRT)276Dcr) may be bred together.
When using the Rag1-/- mFcRn-/- hFcRn Tg 276 mouse strain in a publication, please cite the originating article(s) and include JAX stock #016919 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Homozygous for Rag1<tm1Mom> , Homozygous for Fcgrt<tm1Dcr>,Hemizygous for Tg(CAG-FCGRT)276Dcr |
Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.
The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
What information were you hoping to find through your search?
How easy was it to find what you were looking for?
We may wish to follow up with you. Enter your email if you are happy for us to connect and reachout to you with more questions.
Please Enter a Valid Email Address
Thank you for sharing your feedback! We are working on improving the JAX Mice search. Come back soon for exciting changes.