Overview

Also Known As:Rag1-/- mFcRn-/- hFcRn Tg 276

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.

Donating Investigator

Dr. Derry Roopenian, The Jackson Laboratory

Genetic overview

Genetic Background	Generation

Rag1^tm1Mom

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Rag1	recombination activating gene 1

Fcgrt^tm1Dcr

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Fcgrt	Fc receptor, IgG, alpha chain transporter

Tg(CAG-FCGRT)276Dcr

Allele Type
Transgenic (Inserted expressed sequence, Humanized sequence)

View Genetics

Research Applications

Cancer Research
Hematological Research
Immunology, Inflammation and Autoimmunity Research
Research Tools
Internal/Organ Research
Virology Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

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.

Development

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 Fcgrt^tm1Dcr 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 (Fcgrt^tm1Dcr; 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-Neo^r 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 Fcgrt^tm1Dcr allele.

Expression Data

Expressed Gene	FCGRT, Fc fragment of IgG receptor and transporter, human
Site of Expression

Control Suggestions

Approximate Controls

Additional Information

Considerations for Choosing Controls

Selected References

Zalevsky J; Chamberlain AK; Horton HM; Karki S; Leung IW; Sproule TJ; Lazar GA; Roopenian DC; Desjarlais JR. 2010. Enhanced antibody half-life improves in vivo activity. Nat Biotechnol 28(2):157-9PubMed: 20081867 MGI: J:161273

View All References

Genetics

Rag1^tm1Mom

Allele Symbol: Rag1^tm1Mom

Allele Name	targeted mutation 1, Peter Mombaerts
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Rag-; Rag^1tm1Mom; RAG-1-; Rag1^-; RAG1^null; 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

Fcgrt^tm1Dcr

Allele Symbol: Fcgrt^tm1Dcr

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.

Tg(CAG-FCGRT)276Dcr

Allele Symbol: Tg(CAG-FCGRT)276Dcr

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.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Rag1^tm1Mom related

Cancer Research
- Toxicology
  - B and T cell deficiency, xenograft/transplant host
Hematological Research
- Immunological Defects
  - B and T cell deficiency
Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - B and T cell deficiency
- T Cell Receptor Signaling Defects
  - B and T cell deficiency
- Inflammation
  - B and T cell deficiency
Research Tools
- Toxicology Research
  - xenograft/transplant host
- Cancer Research
  - B and T cell deficiency, xenograft/transplant host
Internal/Organ Research
- Lymphoid Tissue Defects
  - B and T cell deficiency

Genotype: Fcgrt^tm1Dcr related

Immunology, Inflammation and Autoimmunity Research
- Autoimmunity
- Immunodeficiency
  - defects in humoral immune responses
- CD Antigens, Antigen Receptors, and Histocompatibility Markers
  - genes regulating susceptibility to infectious disease and endotoxin
Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - genes regulating susceptibility to infectious disease and endotoxin

Immunology, Inflammation and Autoimmunity Research
- Lymphoid Tissue Defects
  - B and T cell deficiency
- T Cell Receptor Signaling Defects
  - B and T cell deficiency, xenograft/transplant host
- Inflammation
  - B and T cell deficiency
- CD Antigens, Antigen Receptors, and Histocompatibility Markers
  - genes regulating susceptibility to infectious disease and endotoxin
- Immunodeficiency
  - defects in humoral immune responses
Cancer Research
- Toxicology
  - B and T cell deficiency, xenograft/transplant host
Research Tools
- Cancer Research
  - B and T cell deficiency, xenograft/transplant host
- Toxicology Research
  - xenograft/transplant host
Hematological Research
- Immunological Defects
  - B and T cell deficiency
Virology Research
- Reduced MHC Class I Responses to Specific Viruses

Mammalian Phenotype Terms by Genotype

References

Zalevsky J; Chamberlain AK; Horton HM; Karki S; Leung IW; Sproule TJ; Lazar GA; Roopenian DC; Desjarlais JR. 2010. Enhanced antibody half-life improves in vivo activity. Nat Biotechnol 28(2):157-9PubMed: 20081867 MGI: J:161273

Additional - Fcgrt^tm1Dcr related

Additional - Rag1^tm1Mom related

Additional - Tg(CAG-FCGRT)276Dcr related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Tg(FCGRT) alternate1
- Standard PCR:Fcgrt
- Standard PCR:Rag1Alternate1
- Standard PCR:Fcgrt Alternate1
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, mice homozygous for the FcRn α-chain targeted allele (Fcgrt^tm1Dcr), homozygous for the RAG1^null allele (Rag1^tm1Mom), and hemizygous or homozygous for the hFcRn (276) transgene (Tg(CAG-FCGRT)276Dcr) may be bred together.
- Additional Breeding and Husbandry Support
Citation
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.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Domestic Pricing for

Commercial & For-Profit

Not-For-Profit & Academic

International Pricing for

Commercial & For-Profit

Not-For-Profit & Academic

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Homozygous for Rag1<tm1Mom> , Homozygous for Fcgrt<tm1Dcr>,Hemizygous for Tg(CAG-FCGRT)276Dcr

Payment Terms and Conditions

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's Genotype Promise

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.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

Notice regarding distribution of this strain.

Use of MICE by companies or for-profit entities requires a no-fee JAX Leap License prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:Rag1-/- mFcRn-/- hFcRn Tg 276

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Approximate Controls

Additional Information

Selected References

Rag1tm1Mom

Allele Symbol: Rag1tm1Mom

Fcgrttm1Dcr

Allele Symbol: Fcgrttm1Dcr

Tg(CAG-FCGRT)276Dcr

Allele Symbol: Tg(CAG-FCGRT)276Dcr

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Rag1tm1Mom related

Genotype: Fcgrttm1Dcr related

Mammalian Phenotype Terms by Genotype

References

Additional - Fcgrttm1Dcr related

Additional - Rag1tm1Mom related

Additional - Tg(CAG-FCGRT)276Dcr related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Rag1^tm1Mom

Allele Symbol: Rag1^tm1Mom

Fcgrt^tm1Dcr

Allele Symbol: Fcgrt^tm1Dcr

Genotype: Rag1^tm1Mom related

Genotype: Fcgrt^tm1Dcr related

Additional - Fcgrt^tm1Dcr related

Additional - Rag1^tm1Mom related