Overview

Also Known As:FcRn-/- hFcRn (line 276) Tg scid

FcRn-/- hFcRn (line 276) Tg scid mice express a human alpha chain FCGRT molecule in lieu of the endogenous mouse Fcgrt. The presence of the Prkdc^scid allele conveys immunodeficiency. These mice are useful in applications involving xenograft studies, in evaluating the pharmacokinetics and pharmacodynamics of human immunoglobulin (Ig) and Fc-domain based therapeutics, and for testing of potential immunogenic human IgGs.

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Donating Investigator

Dr. Derry Roopenian, The Jackson Laboratory

Genetic overview

Genetic Background	Generation

Prkdc^scid

Allele Type	Gene Symbol	Gene Name
Spontaneous	Prkdc	protein kinase, DNA activated, catalytic polypeptide

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

Research Tools
Internal/Organ Research
Immunology, Inflammation and Autoimmunity Research
Virology Research
Cell Biology Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

View Price List

Details

Detailed Description

These mice are homozygous for a FcRn alpha-chain knockout allele (Fcgrt^tm1Dcr), the Prkdc^scid allele, and express a human FcRn alpha-chain (FCGRT) transgene under the control of the CAG promoter/enhancer (line 276). Mice display a normal level of murine serum albumin, and a low level of murine IgG due to species-specific binding of IgG by human FCGRT, i.e. murine IgG has a very low affinity to human FCGRT and therefore is not recycled. The transgenic founder line 276 provides a model to study serum half-life of human IgG (hIgG), with a good correlation to cynomolgus monkey and human. This mouse model is useful for studying human FcRn biology and the behavior of IgG antibodies and Fc-domain proteins. These immunocompromised, humanized mice produce no mature T cells or B cells and may be useful in xenograft studies, for testing of potential immunogenic hIgGs, and in evaluating the pharmacokinetics of human immunoglobulin and Fc-domain based therapeutics.

Development

These knockout/transgenic mice were generated in the laboratory of Dr. Derry Roopenian (The Jackson Laboratory) by crossing B6.Cg-Fcgrt^tm1Dcr Tg(CAG-FCGRT)279Dcr/DcrJ mice (Stock No. 004919) to B6.Cg-Fcgrt^tm1Dcr Prkdc^scid/DcrJ (Stock No. 018541).

To generate the FcRn alpha-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 (Roopenian et al. J Immunol. 2003 Apr 1;170(7):3528-33).

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. 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 (B6.Cg-Fcgrt^tm1Dcr Tg(CAG-FCGRT)279Dcr/DcrJ, see also Stock No. 004919).
Prkdc^scid occurred spontaneously in a colony of BALB/c-Ighb (C.B-17) mice maintained at the Institute for Cancer Research in Philadelphia, PA. The mutation was transferred to the C57BL/6J background by an initial cross between C.B-17-Prkdc^scid/Prkdc^scid and C57BL/6J followed by sequential backcrossing of heterozygous animals of the F1 and male heterozygotes (identified by test crossing) of subsequent generations to C57BL/6J. At the 10th backcross generation the mutation was made homozygous by brother-sister inbreeding (Stock No. 001913).

Expression Data

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

Control Suggestions

018541 B6.Cg-Fcgrt^tm1Dcr Prkdc^scid/DcrJ

Additional Information

Considerations for Choosing Controls

Selected References

Araki R; Fujimori A; Hamatani K; Mita K; Saito T; Mori M; Fukumura R; Morimyo M; Muto M; Itoh M; Tatsumi K; Abe M. 1997. Nonsense mutation at Tyr-4046 in the DNA-dependent protein kinase catalytic subunit of severe combined immune deficiency mice. Proc Natl Acad Sci U S A 94(6):2438-43PubMed: 9122213 MGI: J:39329
Chaudhury C; Mehnaz S; Robinson JM; Hayton WL; Pearl DK; Roopenian DC; Anderson CL. 2003. The major histocompatibility complex-related Fc receptor for IgG (FcRn) binds albumin and prolongs its lifespan. J Exp Med 197(3):315-22PubMed: 12566415 MGI: J:110885
Petkova SB; Akilesh S; Sproule TJ; Christianson GJ; Al Khabbaz H; Brown AC; Presta LG; Meng YG; Roopenian DC. 2006. Enhanced half-life of genetically engineered human IgG1 antibodies in a humanized FcRn mouse model: potential application in humorally mediated autoimmune disease. Int Immunol 18(12):1759-69PubMed: 17077181 MGI: J:133048
Roopenian DC; Christianson GJ; Sproule TJ; Brown AC; Akilesh S; Jung N; Petkova S; Avanessian L; Choi EY; Shaffer DJ; Eden PA; Anderson CL. 2003. The MHC class I-like IgG receptor controls perinatal IgG transport, IgG homeostasis, and fate of IgG-Fc-coupled drugs. J Immunol 170(7):3528-33PubMed: 12646614 MGI: J:94189

View All References

Genetics

Prkdc^scid

Allele Symbol: Prkdc^scid

Allele Name	severe combined immunodeficiency
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-Igh^b/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*).

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: Prkdc^scid related

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
Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - B and T cell deficiency
Virology Research
- B and T Cell Deficiency
  - AIDS research tool

Genotype: Fcgrt^tm1Dcr related

Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - defects in humoral immune responses
- Autoimmunity
- 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

Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - genes regulating susceptibility to infectious disease and endotoxin
  - MHC class I deficiency
  - B and T cell deficiency
Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - B and T cell deficiency
  - MHC class I deficiency
- CD Antigens, Antigen Receptors, and Histocompatibility Markers
  - genes regulating susceptibility to infectious disease and endotoxin
Virology Research
- Reduced MHC Class I Responses to Specific Viruses
Cell Biology Research
- Channel and Transporter Defects

Mammalian Phenotype Terms by Genotype

References

Araki R; Fujimori A; Hamatani K; Mita K; Saito T; Mori M; Fukumura R; Morimyo M; Muto M; Itoh M; Tatsumi K; Abe M. 1997. Nonsense mutation at Tyr-4046 in the DNA-dependent protein kinase catalytic subunit of severe combined immune deficiency mice. Proc Natl Acad Sci U S A 94(6):2438-43PubMed: 9122213 MGI: J:39329
Chaudhury C; Mehnaz S; Robinson JM; Hayton WL; Pearl DK; Roopenian DC; Anderson CL. 2003. The major histocompatibility complex-related Fc receptor for IgG (FcRn) binds albumin and prolongs its lifespan. J Exp Med 197(3):315-22PubMed: 12566415 MGI: J:110885
Petkova SB; Akilesh S; Sproule TJ; Christianson GJ; Al Khabbaz H; Brown AC; Presta LG; Meng YG; Roopenian DC. 2006. Enhanced half-life of genetically engineered human IgG1 antibodies in a humanized FcRn mouse model: potential application in humorally mediated autoimmune disease. Int Immunol 18(12):1759-69PubMed: 17077181 MGI: J:133048
Roopenian DC; Christianson GJ; Sproule TJ; Brown AC; Akilesh S; Jung N; Petkova S; Avanessian L; Choi EY; Shaffer DJ; Eden PA; Anderson CL. 2003. The MHC class I-like IgG receptor controls perinatal IgG transport, IgG homeostasis, and fate of IgG-Fc-coupled drugs. J Immunol 170(7):3528-33PubMed: 12646614 MGI: J:94189

Additional - Fcgrt^tm1Dcr related

Additional - Prkdc^scid related

Additional - Tg(CAG-FCGRT)276Dcr related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Tg(FCGRT) alternate1
- End Point Analysis:Prkdc End Point
- Standard PCR:Fcgrt
- Standard PCR:Fcgrt Alternate1
- QPCR:Tg(FCGRT)-qPCR
- Standard PCR:Fcgrttm1Dcr Alternate1
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice can be bred as homozygotes for the Fcgrt^tm1Dcr and Prkdc^scid alleles and the Tg(CAG-FCGRT)279Dcr transgene.
- Additional Breeding and Husbandry Support
Citation
When using the FcRn-/- hFcRn (line 276) Tg scid mouse strain in a publication, please cite the originating article(s) and include JAX stock #021146 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
	Heterozygous for Fcgrt<tm1Dcr, Heterozygous for Prkdc<scid>, Hemizygous for Tg(CAG-FCGRT)276Dcr,

Related Products and Services

Frozen Mouse Embryo	B6.Cg-Fcgrt<tm1Dcr> Prkdc<scid> Tg(CAG-FCGRT)276Dcr/DcrJ	$2595.00
Frozen Mouse Embryo	B6.Cg-Fcgrt<tm1Dcr> Prkdc<scid> Tg(CAG-FCGRT)276Dcr/DcrJ	$2595.00
Frozen Mouse Embryo	B6.Cg-Fcgrt<tm1Dcr> Prkdc<scid> Tg(CAG-FCGRT)276Dcr/DcrJ	$3373.50
Frozen Mouse Embryo	B6.Cg-Fcgrt<tm1Dcr> Prkdc<scid> Tg(CAG-FCGRT)276Dcr/DcrJ	$3373.50

Payment Terms and Conditions

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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

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:FcRn-/- hFcRn (line 276) Tg scid

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Prkdcscid

Allele Symbol: Prkdcscid

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: Prkdcscid related

Genotype: Fcgrttm1Dcr related

Mammalian Phenotype Terms by Genotype

References

Additional - Fcgrttm1Dcr related

Additional - Prkdcscid 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

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Prkdc^scid

Allele Symbol: Prkdc^scid

Fcgrt^tm1Dcr

Allele Symbol: Fcgrt^tm1Dcr

Genotype: Prkdc^scid related

Genotype: Fcgrt^tm1Dcr related

Additional - Fcgrt^tm1Dcr related

Additional - Prkdc^scid related