Overview

FcRn-deficient hFcRn(Tg99) BXSB.Yaa mice (BXSB.FcRn-/- hFcRn(Tg99) or BXSB.Yaa FcRn-/- hFcRn(Tg99)) are a BXSB-congenic strain with endogenous mouse FcRn expression knocked out and replaced with expression of the human FcRn α-chain transgene under the control of its natural human promoter. These mice may be useful in evaluating thepharmacokinetics/pharmacodynamics of human immunoglobulin G and/or human therapeutic antibodies in an autoimmune disease setting.

Donating Investigator

Dr. Derry Roopenian, The Jackson Laboratory

Genetic overview

Genetic Background	Generation

Yaa

Allele Type	Gene Symbol	Gene Name
Spontaneous	Yaa	accelerated autoimmunity and lymphoproliferation transposition

Fcgrt^tm1Dcr

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

Tg(FCGRT)99Dcr

Allele Type
Transgenic (Inserted expressed sequence, Humanized sequence)

View Genetics

Research Applications

Immunology, Inflammation and Autoimmunity Research
Research Tools
Mouse/Human Gene Homologs

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

BXSB/MpJ inbred males (Stock No. 000740) develop a spontaneous lupus-like autoimmune syndrome: mortality starts at ~13 weeks of age with 50% lethality by ~30 weeks and 76% lethality by ~40 weeks. BXSB/MpJ inbred females develop a greatly attenuated form of autoimmune disease because they lack Yaa.

BXSB.FcRn-/- mice are described and available as Stock No. 021455. Mice homozygous for the FcRn knockout allele (FcRn-/-) lack the Fc receptor (FcRn), which normally functions to enhance the presentation of immune-complexed antigens by MHC class II molecules and is critical for maintaining normal concentrations of immunoglobulin G (IgG) antibodies and serum albumin. BXSB.FcRn-/- mice are viable and fertile, with ~50% reduction in IgG. Both homozygous and heterozygous mice develop spontaneous lupus-like autoimmune syndrome similarly to BXSB/MpJ inbred mice.

Stock No. 025099: FcRn-deficient hFcRn(Tg99) BXSB.Yaa mice (BXSB.FcRn-/- hFcRn(Tg99) or BXSB.Yaa FcRn-/- hFcRn(Tg99)) are a BXSB-congenic strain with endogenous mouse FcRn expression knocked out and replaced with expression of the human FcRn α-chain transgene under the control of its natural human promoter. Mice homozygous for the FcRn null allele and hemizygous for the hFcRn(Tg99) transgene (FcRn-/- hFcRn(Tg99)) are viable and fertile. The donating investigator reports that FcRn-/- hFcRn(Tg99) animals develop spontaneous lupus-like autoimmune syndrome similarly to that of BXSB.FcRn-/- mice and BXSB/MpJ inbred mice. While the phenotype of FcRn-/- hFcRn(Tg99) mice is not fully characterized to date (June 2014), they may be expected to have reduced IgG levels. Because human FcRn protects human IgG and does not protect mouse IgG, these FcRn-/- hFcRn(Tg99) mice are ideal for evaluating the pharmacokinetics/pharmacodynamics of human therapeutic antibodies in an autoimmune disease setting.

Of note, C57BL/6J-congenic mice harboring the FcRn null allele and the same transgene with different insertion site [hFcRn(Tg32)] are described and available from The Jackson Laboratory Repository as Stock No. 014565.

Development

BXSB.FcRn-/- hFcRn(Tg99) mice are a BXSB-congenic "humanized" FcRn strain; carrying the FcRn null allele and a transgene expressing human FcRn. The knockout mutation and human transgene are described below.

The FcRn knockout allele (FcRn^-; Fcgrt^tm1Dcr) was designed by Dr. Derry C. Roopenian (The Jackson Laboratory) to replace 1588 nucleotides (encoding promoter sequence 5' of the transcriptional start site, exon1, intron 2, and most of exon2) of the Fcgrt gene (Fc receptor, IgG, alpha chain transporter) on chromosome 7 with a PGK-Neo^r cassette. The vector was electroporated into 129X1/SvJ-derived ESV/J-1182 (RW4) embryonic stem cells. FcRn^- mice backcrossed for at least 12 generations onto the BXSB/MpJ genetic background (BXSB.FcRn^-) are described and available as Stock No. 021455. BXSB.FcRn^- mice were used for breeding as below.

The hFcRn transgenic line 99 [hFcRn(Tg99)] mice were created by Dr. Roopenian. It has the same transgene construct as hFcRn transgenic line 32 (Stock No. 014565). The transgene genomic insertion sites of line 99 and line 32 are not characterized to date. The hFcRn transgene is an ~34 kbp cosmid clone with the complete ~11 kbp human FCGRT gene (as well as ~10 kbp of 5' and 3' flanking sequences). This construct was microinjected into fertilized BXSB/MpJ mouse eggs. Founder animal Tg#99 was bred to BXSB/MpJ. The resulting transgenic colony was maintained on the BXSB/MpJ genetic background by breeding transgenic mice together for several generations. These BXSB.hFcRn(Tg99) mice were used for breeding as below.

To generate the BXSB.FcRn^- hFcRn(Tg99) animals (Stock No. 025099), The Jackson Laboratory Repository Autoimmune Resource bred BXSB.FcRn^- and BXSB.hFcRn(Tg99) together. Male mice have the BXSB/MpJ-derived Y chromosome that contains the Y-linked autoimmune accelerator locus (Yaa).

Expression Data

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

Control Suggestions

Noncarrier

Approximate Controls

Depending upon the experiment, the following may be appropriate control strain(s):
BXSB.FcRn-/-, non-carrier Tg(FCGRT)mice
BXSB/MpJ inbred mice (Stock No. 000740).
000740 BXSB/MpJ

Additional Information

Considerations for Choosing Controls

Selected References

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

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Genetics

Yaa

Allele Symbol: Yaa

Allele Name	accelerated autoimmunity and lymphoproliferation
Allele Type	Spontaneous
Allele Synonym(s)	Is(XOfd1-Mid1;Y)1Mp; Tp(X;Y)1Ekw
Gene Symbol and Name	Yaa, accelerated autoimmunity and lymphoproliferation transposition
Gene Synonym(s)
Strain of Origin	SB/Le
Chromosome	Y
Molecular Note	An approximately 4 MB region of the X chromosome that includes at least 13 known genes (spanning from Ofd1 to Mid1) was translocated to the Y chromosome adjacent to the pseudoautosomal region. Increased RNA expression of Msl3, Tlr7, Tmsb4x and Rab9 was detected in follicular B cells.

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(FCGRT)99Dcr

Allele Symbol: Tg(FCGRT)99Dcr

Allele Name	transgene insertion 99, Derry C Roopenian
Allele Type	Transgenic (Inserted expressed sequence, Humanized sequence)
Allele Synonym(s)	hFcRn(Tg99)
Gene Symbol and Name	Tg(FCGRT)99Dcr, transgene insertion 99, Derry C Roopenian
Gene Synonym(s)
Promoter	FCGRT, Fc fragment of IgG receptor and transporter, human
Expressed Gene	FCGRT, Fc fragment of IgG receptor and transporter, human
Strain of Origin	BXSB/MpJ
Chromosome	UN
Molecular Note	A 34Kb fragment of a BAC containing the entire human FCGRT , Fc fragment of IgG, receptor, transporter, alpha, gene (approximately 11kb) and approximately 10kb of flanking sequence was sublconed into a SuperCos vector. Founder line 99 was established.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Genotype: Yaa related

Immunology, Inflammation and Autoimmunity Research
- Autoimmunity
  - lupus erythematosus

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

Immunology, Inflammation and Autoimmunity Research
- Autoimmunity
  - lupus erythematosus, control
  - lupus erythematosus
- Growth Factors/Receptors/Cytokines
- CD Antigens, Antigen Receptors, and Histocompatibility Markers
  - genes regulating susceptibility to infectious disease and endotoxin
- Immunodeficiency
  - defects in humoral immune responses
Mouse/Human Gene Homologs
- systemic lupus erythematosus
Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - genes regulating susceptibility to infectious disease and endotoxin

Mammalian Phenotype Terms by Genotype

References

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 - Tg(FCGRT)99Dcr related

Additional - Yaa related

Technical Support

CONTACT TECHNICAL SUPPORT

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

To maintain the live colony, mice homozygous for the FcRn null allele and hemizygous for the hFcRn(Tg99) transgene (FcRn-/- hFcRn(Tg99)) may be bred to mice homozygous for the FcRn null allele and wildtype (noncarrier) for the hFcRn(Tg99) transgene. Both FcRn-/- hFcRn(Tg99) and FcRn+/- hFcRn(Tg99) mice develop spontaneous lupus-like autoimmune syndrome similarly to BXSB/MpJ inbred mice (Stock No. 000740): mortality in males starts at ~13 weeks of age with 50% lethality by ~30 weeks and 76% lethality by ~40 weeks. Females develop a greatly attenuated form of autoimmune disease because they lack Yaa. The expected coat color is white-bellied agouti.
- Additional Breeding and Husbandry Support
Citation
When using the BXSB.Cg-Fcgrt^tm1Dcr Tg(FCGRT)99Dcr/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #025099 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>, Hemizygous or non carrier for Tg(FCGRT)99Dcr

Related Products and Services

Frozen Mouse Embryo	BXSB.Cg-Fcgrt<tm1Dcr> Tg(FCGRT)99Dcr/J	$2595.00
Frozen Mouse Embryo	BXSB.Cg-Fcgrt<tm1Dcr> Tg(FCGRT)99Dcr/J	$2595.00
Frozen Mouse Embryo	BXSB.Cg-Fcgrt<tm1Dcr> Tg(FCGRT)99Dcr/J	$3373.50
Frozen Mouse Embryo	BXSB.Cg-Fcgrt<tm1Dcr> Tg(FCGRT)99Dcr/J	$3373.50

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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

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Approximate Controls

Additional Information

Selected References

Yaa

Allele Symbol: Yaa

Fcgrttm1Dcr

Allele Symbol: Fcgrttm1Dcr

Tg(FCGRT)99Dcr

Allele Symbol: Tg(FCGRT)99Dcr

Disease Terms

Research Areas By Phenotype

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

Genotype: Yaa related

Genotype: Fcgrttm1Dcr related

Mammalian Phenotype Terms by Genotype

References

Additional - Fcgrttm1Dcr related

Additional - Tg(FCGRT)99Dcr related

Additional - Yaa 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

Fcgrt^tm1Dcr

Allele Symbol: Fcgrt^tm1Dcr

Genotype: Fcgrt^tm1Dcr related

Additional - Fcgrt^tm1Dcr related