NSG FcRn-/- hFcRn (276) Tg mice are NOD.scid.Il2Rγcnull ("NSG") animals with a humanized FcRn α-chain (FcRn-/- hFcRn line 276 Tg). Homozygous NSG FcRn-/- hFcRn (276) Tg mice have no mature T cells or B cells, lack functional natural killer (NK) cells, are deficient in cytokine signaling, and express human FcRn in place of the endogenous mouse FcRn. These mice may be useful in evaluating the pharmacokinetics/pharmacodynamics of human immunoglobulin G in transplantation studies, human tumor xenografts and mouse tumor allografts. For example, examining the ability of anti-FcRn to inhibit angiogenesis and other tumor/stroma interactions.
Dr. Derry Roopenian, The Jackson Laboratory
Dr. Leonard D. Shultz, The Jackson Laboratory
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Spontaneous | Prkdc | protein kinase, DNA activated, catalytic polypeptide |
Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Il2rg | interleukin 2 receptor, gamma chain |
Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Fcgrt | Fc receptor, IgG, alpha chain transporter |
Allele Type |
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Transgenic (Inserted expressed sequence, Humanized sequence) |
NSG FcRn-/- hFcRn (276) Tg mice are NOD.scid.Il2Rγcnull ("NSG") animals with a humanized FcRn α-chain (FcRn-/- hFcRn line 276 Tg).
NSG FcRn-/- hFcRn (276) Tg females homozygous for all three mutations and the transgene, and males homozygous for scid, homozygous for FcRn null, hemizygous for the X-linked Il2Rγcnull and homozygous for the hFcRn(276) transgene may be collectively referred to as homozygous NSG FcRn-/- hFcRn (276) Tg mice.
Although viable and fertile, homozygous NSG FcRn-/- hFcRn (276) Tg mice are immunodeficient: they have no mature T cells or B cells, lack functional natural killer (NK) cells and are deficient in cytokine signaling. They have endogenous FcRn α-chain expression deleted and replaced a human FcRn α-chain (FCGRT) transgene under control of CAG hybrid promoter.
For additional information on the phenotype of FcRn-/- hFcRn (276) Tg mice, see Stock No. 004919.
Similar to other immunodeficient strains, maintaining homozygous NSG FcRn-/- hFcRn (276) Tg mice in high health status (specific pathogen-free) vivaria promotes overall colony health. If homozygous NSG FcRn-/- hFcRn (276) Tg animals are maintained in low health barrier rooms, the use of medicated water (e.g., sulfatrim/trimethoprim-sulfa or enrofloxacin/Baytril) is suggested to increase overall colony health.
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Resources for the NSG mouse model, including discussion forum, immunodeficient model comparison, and categorized, up-to-date references.
NSG FcRn-/- hFcRn (276) Tg mice are NOD.scid.Il2Rγcnull ("NSG") animals with the FcRn knock-out allele and the hFcRn (276) transgene expressing human FcRn α-chain. Each mutation/transgene are described below.
NSG mice are non-obese diabetic animals (NOD/ShiLtJ) harboring the spontaneous severe combined immunodeficiency mutation (Prkdcscid) on chromosome 16 and the Il2Rγcnull mutation at ~101 Mbp on the X chromosome (Il2rgtm1Wjl created by Dr. Warren J. Leonard [NIH]). NSG mice are described and available from The Jackson Laboratory Repository as Stock No. 005557.
The FcRn α-chain knock-out allele (Fcgrttm1Dcr) was generated in the laboratory of Dr. Derry Roopenian (The Jackson Laboratory), and is described for Stock No. 003982. Briefly, it has 1588 nucleotides (encoding promoter sequence 5' of the transcriptional start site, exon1, intron 2, and most of exon2) replaced with a PGK-Neor cassette.
The hFcRn (276) transgene (Tg(CAG-FCGRT)276Dcr) was generated in the laboratory of Dr. Derry Roopenian (The Jackson Laboratory), and is described for Stock No. 004919. Briefly, the 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 (FCGRT), 0.73 kb rabbit beta-globin intron, and 0.35 kb SV40 polyA sequence.
In 2016, some C57BL/6J-congenic FcRn-/- hFcRn (276) Tg mice (from Stock No. 004919) were bred to NSG mice (from Stock No. 005557) for five generations. The resulting NSG FcRn-/- hFcRn (276) Tg mice were bred together for several generations, and then made available as Stock No. 028616. In November 2017, SNP analyses show the colony to be greater than 97% NOD.
Expressed Gene | FCGRT, Fc fragment of IgG receptor and transporter, human |
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Site of Expression |
Depending upon the experiment, the following may be appropriate control strain(s):
--NOD.scid.IL2RγcKO ("NSG"; Stock No. 005557)
--NOD.scid (Stock No. 001303)
--NOD/ShiLtJ inbred mice (Stock No. 001976)
--FcRn-/- hFcRn (276) Tg (Stock No. 004919)
--FcRn-/- on NOD (Stock No. 003988)
Allele Name | severe combined immunodeficiency |
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Allele Type | Spontaneous |
Allele Synonym(s) | SCID |
Gene Symbol and Name | Prkdc, protein kinase, DNA activated, catalytic polypeptide |
Gene Synonym(s) | |
Site of Expression | T and B lymphocytes. |
Strain of Origin | C.BKa-Ighb/Icr |
Chromosome | 16 |
Molecular Note | A T-to-A transversion point mutation at a position corresponding to codon 4046 (codon 4095 in transcript ENSMUST00000023352.8) created a premature stop codon (p.Y4046*). |
Allele Name | targeted mutation 1, Warren J Leonard |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | [KO]gammac; CD132-; gammac-; gc-; Il2rgtm1Wjll; IL2Rgammanull |
Gene Symbol and Name | Il2rg, interleukin 2 receptor, gamma chain |
Gene Synonym(s) | |
Site of Expression | Primarily lymphoid cells. |
Strain of Origin | 129S4/SvJae |
Chromosome | X |
Molecular Note | A neomycin resistance cassette replaced part of exon 3 and all of exons 4 - 8 of the gene, resulting in the loss of most of the extracellular domain and all of the transmembrane and cytoplasmic domains of the protein. |
Mutations Made By | Dr. Warren Leonard, NHLBI, NIH |
Allele Name | targeted mutation 1, Derry C Roopenian |
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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 |
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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. |
NSG FcRn-/- hFcRn (276) Tg females homozygous for all three mutations and the transgene, and males homozygous for scid, homozygous for FcRn null, hemizygous for the X-linked Il2Rγcnull and homozygous for the hFcRn(276) transgene may be collectively referred to as homozygous NSG FcRn-/- hFcRn (276) Tg mice. When maintaining a live colony, homozygous NSG FcRn-/- hFcRn (276) Tg females may be bred with homozygous NSG FcRn-/- hFcRn (276) Tg males.
Homozygous NSG FcRn-/- hFcRn (276) Tg mice are immunodeficient. As such, and similar to other immunodeficient strains, maintenance in high health status (specific pathogen-free) vivaria promotes overall colony health. If homozygous NSG FcRn-/- hFcRn (276) Tg animals are maintained in low health barrier rooms, the use of medicated water (e.g., sulfatrim/trimethoprim-sulfa or enrofloxacin/Baytril) is suggested to increase overall colony health.
When using the NSG FcRn-/- hFcRn (276) Tg mouse strain in a publication, please cite the originating article(s) and include JAX stock #028616 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Heterozygous for Fcgrt<tm1Dcr> Heterozygous for Prkdc<scid> Heterozygous for Il2rg<tm1Wjl> Hemizygous for Tg(CAG-FCGRT) females orHeterozygous for Fcgrt<tm1Dcr> Heterozygous for Prkdc<scid> Wildtype for Il2rg<tm1Wjl> Hemizygous for Tg(CAG-FCGRT) males |
Frozen Mouse Embryo | NOD.Cg-Tg(CAG-FCGRT)276Dcr Fcgrt<tm1Dcr> Prkdc<scid> Il2rg<t | $2595.00 |
Frozen Mouse Embryo | NOD.Cg-Tg(CAG-FCGRT)276Dcr Fcgrt<tm1Dcr> Prkdc<scid> Il2rg<t | $2595.00 |
Frozen Mouse Embryo | NOD.Cg-Tg(CAG-FCGRT)276Dcr Fcgrt<tm1Dcr> Prkdc<scid> Il2rg<t | $3373.50 |
Frozen Mouse Embryo | NOD.Cg-Tg(CAG-FCGRT)276Dcr Fcgrt<tm1Dcr> Prkdc<scid> Il2rg<t | $3373.50 |
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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.
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