Strain Name:

B6.129X1-Fcgrttm1Dcr/DcrJ

Stock Number:

003982

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Availability:

Repository- Live

FcRn knock-out mice are unable to recycle IgG or albumin and degrade IgG at an accelerated rate, resulting in low plasma expression levels of both. Further, they are unable to transport IgG across epithelial barriers (e.g., neonatal gut and placenta), allowing for the study of maternal passive immunity. This model may be useful in testing therapeutic compounds and their involvement in the FcRn pathway, or as a control for humanized FcRn transgenics.

Description

Strain Information

Former Names B6.129X1-Fcgrttm1Dcr/Dcr    (Changed: 18-MAR-08 )
B6.129X1-Fcgrttm1Dcr    (Changed: 09-MAY-06 )
B6;129X1-Fcgrttm1Dcr    (Changed: 15-DEC-04 )
Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Mating SystemHomozygote x Homozygote         (Female x Male)   02-DEC-11
Specieslaboratory mouse
GenerationN11F12p+F9 (11-MAY-11)
Generation Definitions

Description
The neonatal Fc receptor (FcRn), encoded by the Fcgrt gene, is a MHC class I like molecule. One of its functions is to protect IgG and albumin from degradation, and to mediate the transport of IgG across epithelial cells. Further, it is plays a role in antigen presentation by professional antigen presenting cells. It has been demonstrated that FcRn is critical for the materno-fetal transport and intestinal uptake of IgG.

Homozygous FcRn α-chain knockout mice are viable and fertile. No gene product (mRNA or protein) is detected by quantitative PCR analysis of liver cDNA or Western blot analysis of small intestine from homozygotes. Homozygotes exhibit plasma albumin concentration approximately 45% of levels observed in wild-type controls, reduced IgG levels, as well as diminished perinatal maternal IgG transport. FcRn -/- mice are resistant to experimentally induced, serum-transfer autoimmune arthritis, as well as experimentally induced bullous pemphigoid, pemphigus foliaceus, and pemphigus vulgaris. Homozygotes are more sensitive to experimentally induced Lyme's disease arthritis, with more severe ankle swelling, joint involvement and decreased anti Borrelia burgdorferi antibody serum levels. IgG accumulates in the glomerular basement membranes of aging mutants, and clearance of IgG from the kidneys is impaired. This strain may be useful in studies of IgG-mediated autoimmune diseases, IgG homeostasis, IgG-mediated phagocytosis and maternal passive immunity and serves as a control for humanized FcRn transgenics (see Stock Numbers: 004919 and 014565)

Development
A targeting vector was designed to replace 1588 nucleotide fragments (encoding promoter sequence 5' of the transcriptional start site, exon 1, intron 2, and most of exon 2) with a PGK-Neor cassette. The vector was electroporated into 129X1/SvJ-derived ESV/J-1182 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient C57BL/6J blastocysts. The resulting chimeric animals were crossed to C57BL/6J mice. The mice were then backcrossed to C57BL/6J for 11 generations.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

View Strains carrying   Fcgrttm1Dcr     (13 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Fcgrttm1Dcr/Fcgrttm1Dcr

        B6.129X1-Fcgrttm1Dcr/DcrJ
  • homeostasis/metabolism phenotype
  • decreased circulating serum albumin level   (MGI Ref ID J:110885)
  • immune system phenotype
  • decreased IgG level   (MGI Ref ID J:110885)
  • hematopoietic system phenotype
  • decreased IgG level   (MGI Ref ID J:110885)

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Fcgrttm1Dcr/Fcgrttm1Dcr

        either: 129 or (involves: 129 * C57BL/6)
  • immune system phenotype
  • decreased IgG level
    • failure of perinatal IgG from mothers to newborns   (MGI Ref ID J:94189)
    • levels of maternal IgGs lowered in homozygous pups about 190 fold   (MGI Ref ID J:94189)
    • serum half life of IgG1 segnificantly reduced, 1.4 days as opposed to 9 days   (MGI Ref ID J:94189)
    • specific IgG memory response to antigen challenge is significantly reduced   (MGI Ref ID J:94189)
  • hematopoietic system phenotype
  • decreased IgG level
    • failure of perinatal IgG from mothers to newborns   (MGI Ref ID J:94189)
    • levels of maternal IgGs lowered in homozygous pups about 190 fold   (MGI Ref ID J:94189)
    • serum half life of IgG1 segnificantly reduced, 1.4 days as opposed to 9 days   (MGI Ref ID J:94189)
    • specific IgG memory response to antigen challenge is significantly reduced   (MGI Ref ID J:94189)
View Research Applications

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

Cell Biology Research
Channel and Transporter Defects

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

Neurobiology Research
Channel and Transporter Defects

Fcgrttm1Dcr related

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

Research Tools
Immunology, Inflammation and Autoimmunity Research
      genes regulating susceptibility to infectious disease and endotoxin

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Fcgrttm1Dcr
Allele Name targeted mutation 1, Derry C Roopenian
Allele Type Targeted (Null/Knockout)
Common Name(s) FcRn-;
Strain of Origin129X1/SvJ
ES Cell Line NameRW-4
ES Cell Line Strain129X1/SvJ
Gene Symbol and Name Fcgrt, Fc receptor, IgG, alpha chain transporter
Chromosome 7
Gene Common Name(s) FCRN; alpha-chain; neonatal Fc receptor;
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. [MGI Ref ID J:94189]

Genotyping

Genotyping Information

Genotyping Protocols

Fcgrttm1Dcr, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Fcgrttm1Dcr related

Akilesh S; Christianson GJ; Roopenian DC; Shaw AS. 2007. Neonatal FcR expression in bone marrow-derived cells functions to protect serum IgG from catabolism. J Immunol 179(7):4580-8. [PubMed: 17878355]  [MGI Ref ID J:152349]

Akilesh S; Huber TB; Wu H; Wang G; Hartleben B; Kopp JB; Miner JH; Roopenian DC; Unanue ER; Shaw AS. 2008. Podocytes use FcRn to clear IgG from the glomerular basement membrane. Proc Natl Acad Sci U S A 105(3):967-72. [PubMed: 18198272]  [MGI Ref ID J:131366]

Akilesh S; Petkova S; Sproule TJ; Shaffer DJ; Christianson GJ; Roopenian D. 2004. The MHC class I-like Fc receptor promotes humorally mediated autoimmune disease. J Clin Invest 113(9):1328-33. [PubMed: 15124024]  [MGI Ref ID J:95104]

Andersen JT; Foss S; Kenanova VE; Olafsen T; Leikfoss IS; Roopenian DC; Wu AM; Sandlie I. 2012. Anti-carcinoembryonic antigen single-chain variable fragment antibody variants bind mouse and human neonatal Fc receptor with different affinities that reveal distinct cross-species differences in serum half-life. J Biol Chem 287(27):22927-37. [PubMed: 22570488]  [MGI Ref ID J:188378]

Bai Y; Ye L; Tesar DB; Song H; Zhao D; Bjorkman PJ; Roopenian DC; Zhu X. 2011. Intracellular neutralization of viral infection in polarized epithelial cells by neonatal Fc receptor (FcRn)-mediated IgG transport. Proc Natl Acad Sci U S A 108(45):18406-11. [PubMed: 22042859]  [MGI Ref ID J:180229]

Baker K; Qiao SW; Kuo TT; Aveson VG; Platzer B; Andersen JT; Sandlie I; Chen Z; de Haar C; Lencer WI; Fiebiger E; Blumberg RS. 2011. Neonatal Fc receptor for IgG (FcRn) regulates cross-presentation of IgG immune complexes by CD8-CD11b+ dendritic cells. Proc Natl Acad Sci U S A 108(24):9927-32. [PubMed: 21628593]  [MGI Ref ID J:173310]

Baker K; Rath T; Flak MB; Arthur JC; Chen Z; Glickman JN; Zlobec I; Karamitopoulou E; Stachler MD; Odze RD; Lencer WI; Jobin C; Blumberg RS. 2013. Neonatal Fc receptor expression in dendritic cells mediates protective immunity against colorectal cancer. Immunity 39(6):1095-107. [PubMed: 24290911]  [MGI Ref ID J:209206]

Binstadt BA; Patel PR; Alencar H; Nigrovic PA; Lee DM; Mahmood U; Weissleder R; Mathis D; Benoist C. 2006. Particularities of the vasculature can promote the organ specificity of autoimmune attack. Nat Immunol 7(3):284-92. [PubMed: 16444258]  [MGI Ref ID J:112604]

Chaudhury C; Kim J; Mehnaz S; Wani MA; Oberyszyn TM; Bronson CL; Mohanty S; Hayton WL; Robinson JM; Anderson CL. 2006. Accelerated transferrin degradation in HFE-deficient mice is associated with increased transferrin saturation. J Nutr 136(12):2993-8. [PubMed: 17116709]  [MGI Ref ID J:117735]

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):315-22. [PubMed: 12566415]  [MGI Ref ID J:110885]

Chen P; Li C; Lang S; Zhu G; Reheman A; Spring CM; Freedman J; Ni H. 2010. Animal model of fetal and neonatal immune thrombocytopenia: role of neonatal Fc receptor in the pathogenesis and therapy. Blood 116(18):3660-8. [PubMed: 20647570]  [MGI Ref ID J:166478]

Crow AR; Suppa SJ; Chen X; Mott PJ; Lazarus AH. 2011. The neonatal Fc receptor (FcRn) is not required for IVIg or anti-CD44 monoclonal antibody-mediated amelioration of murine immune thrombocytopenia. Blood 118(24):6403-6. [PubMed: 22001393]  [MGI Ref ID J:179078]

Crowley H; Alroy J; Sproule TJ; Roopenian D; Huber BT. 2006. The MHC class I-related FcRn ameliorates murine Lyme arthritis. Int Immunol 18(3):409-14. [PubMed: 16415101]  [MGI Ref ID J:106617]

Deane R; Sagare A; Hamm K; Parisi M; LaRue B; Guo H; Wu Z; Holtzman DM; Zlokovic BV. 2005. IgG-assisted age-dependent clearance of Alzheimer's amyloid beta peptide by the blood-brain barrier neonatal Fc receptor. J Neurosci 25(50):11495-503. [PubMed: 16354907]  [MGI Ref ID J:103998]

Dumont JA; Liu T; Low SC; Zhang X; Kamphaus G; Sakorafas P; Fraley C; Drager D; Reidy T; McCue J; Franck HW; Merricks EP; Nichols TC; Bitonti AJ; Pierce GF; Jiang H. 2012. Prolonged activity of a recombinant factor VIII-Fc fusion protein in hemophilia A mice and dogs. Blood 119(13):3024-30. [PubMed: 22246033]  [MGI Ref ID J:182551]

Kim J; Bronson CL; Hayton WL; Radmacher MD; Roopenian DC; Robinson JM; Anderson CL. 2006. Albumin turnover: FcRn-mediated recycling saves as much albumin from degradation as the liver produces. Am J Physiol Gastrointest Liver Physiol 290(2):G352-60. [PubMed: 16210471]  [MGI Ref ID J:106048]

Kim J; Mohanty S; Ganesan LP; Hua K; Jarjoura D; Hayton WL; Robinson JM; Anderson CL. 2009. FcRn in the yolk sac endoderm of mouse is required for IgG transport to fetus. J Immunol 182(5):2583-9. [PubMed: 19234152]  [MGI Ref ID J:146267]

Koltun M; Nikolovski J; Strong K; Nikolic-Paterson D; Comper WD. 2005. Mechanism of hypoalbuminemia in rodents. Am J Physiol Heart Circ Physiol 288(4):H1604-10. [PubMed: 15539420]  [MGI Ref ID J:97362]

Letourneau S; van Leeuwen EM; Krieg C; Martin C; Pantaleo G; Sprent J; Surh CD; Boyman O. 2010. IL-2/anti-IL-2 antibody complexes show strong biological activity by avoiding interaction with IL-2 receptor alpha subunit CD25. Proc Natl Acad Sci U S A 107(5):2171-6. [PubMed: 20133862]  [MGI Ref ID J:157531]

Li N; Zhao M; Hilario-Vargas J; Prisayanh P; Warren S; Diaz LA; Roopenian DC; Liu Z. 2005. Complete FcRn dependence for intravenous Ig therapy in autoimmune skin blistering diseases. J Clin Invest 115(12):3440-50. [PubMed: 16284651]  [MGI Ref ID J:104709]

Martin CE; van Leeuwen EM; Im SJ; Roopenian DC; Sung YC; Surh CD. 2013. IL-7/anti-IL-7 mAb complexes augment cytokine potency in mice through association with IgG-Fc and by competition with IL-7R. Blood 121(22):4484-92. [PubMed: 23610371]  [MGI Ref ID J:198495]

McPhee CG; Sproule TJ; Shin DM; Bubier JA; Schott WH; Steinbuck MP; Avenesyan L; Morse HC 3rd; Roopenian DC. 2011. MHC class I family proteins retard systemic lupus erythematosus autoimmunity and B cell lymphomagenesis. J Immunol 187(9):4695-704. [PubMed: 21964024]  [MGI Ref ID J:179430]

Mezo AR; McDonnell KA; Hehir CA; Low SC; Palombella VJ; Stattel JM; Kamphaus GD; Fraley C; Zhang Y; Dumont JA; Bitonti AJ. 2008. Reduction of IgG in nonhuman primates by a peptide antagonist of the neonatal Fc receptor FcRn. Proc Natl Acad Sci U S A 105(7):2337-42. [PubMed: 18272495]  [MGI Ref ID J:132181]

Nakata K; Kobayashi K; Ishikawa Y; Yamamoto M; Funada Y; Kotani Y; Blumberg RS; Karasuyama H; Yoshida M; Nishimura Y. 2010. The transfer of maternal antigen-specific IgG regulates the development of allergic airway inflammation early in life in an FcRn-dependent manner. Biochem Biophys Res Commun 395(2):238-43. [PubMed: 20362552]  [MGI Ref ID J:160346]

Patel DA; Puig-Canto A; Challa DK; Perez Montoyo H; Ober RJ; Ward ES. 2011. Neonatal Fc receptor blockade by Fc engineering ameliorates arthritis in a murine model. J Immunol 187(2):1015-22. [PubMed: 21690327]  [MGI Ref ID J:178025]

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):1759-69. [PubMed: 17077181]  [MGI Ref ID J:133048]

Roopenian DC; Christianson GJ; Sproule TJ. 2010. Human FcRn transgenic mice for pharmacokinetic evaluation of therapeutic antibodies. Methods Mol Biol 602:93-104. [PubMed: 20012394]  [MGI Ref ID J:170668]

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):3528-33. [PubMed: 12646614]  [MGI Ref ID J:94189]

Sarav M; Wang Y; Hack BK; Chang A; Jensen M; Bao L; Quigg RJ. 2009. Renal FcRn reclaims albumin but facilitates elimination of IgG. J Am Soc Nephrol 20(9):1941-52. [PubMed: 19661163]  [MGI Ref ID J:166328]

Stein C; Kling L; Proetzel G; Roopenian DC; de Angelis MH; Wolf E; Rathkolb B. 2011. Clinical chemistry of human FcRn transgenic mice. Mamm Genome :. [PubMed: 22193411]  [MGI Ref ID J:179989]

Stoklasek TA; Colpitts SL; Smilowitz HM; Lefrancois L. 2010. MHC Class I and TCR Avidity Control the CD8 T Cell Response to IL-15/IL-15R{alpha} Complex. J Immunol 185(11):6857-65. [PubMed: 21041729]  [MGI Ref ID J:166134]

Vidarsson G; Stemerding AM; Stapleton NM; Spliethoff SE; Janssen H; Rebers FE; de Haas M; van de Winkel JG. 2006. FcRn: an IgG receptor on phagocytes with a novel role in phagocytosis. Blood 108(10):3573-9. [PubMed: 16849638]  [MGI Ref ID J:140454]

Wang W; Vlasak J; Li Y; Pristatsky P; Fang Y; Pittman T; Roman J; Wang Y; Prueksaritanont T; Ionescu R. 2011. Impact of methionine oxidation in human IgG1 Fc on serum half-life of monoclonal antibodies. Mol Immunol 48(6-7):860-6. [PubMed: 21256596]  [MGI Ref ID J:170957]

Yoshida M; Kobayashi K; Kuo TT; Bry L; Glickman JN; Claypool SM; Kaser A; Nagaishi T; Higgins DE; Mizoguchi E; Wakatsuki Y; Roopenian DC; Mizoguchi A; Lencer WI; Blumberg RS. 2006. Neonatal Fc receptor for IgG regulates mucosal immune responses to luminal bacteria. J Clin Invest 116(8):2142-2151. [PubMed: 16841095]  [MGI Ref ID J:113122]

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):157-9. [PubMed: 20081867]  [MGI Ref ID J:161273]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, these mice can be bred as homozygotes.
Mating SystemHomozygote x Homozygote         (Female x Male)   02-DEC-11
Diet Information LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $177.00Female or MaleHomozygous for Fcgrttm1Dcr  
Price per Pair (US dollars $)Pair Genotype
$354.00Homozygous for Fcgrttm1Dcr x Homozygous for Fcgrttm1Dcr  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $230.10Female or MaleHomozygous for Fcgrttm1Dcr  
Price per Pair (US dollars $)Pair Genotype
$460.20Homozygous for Fcgrttm1Dcr x Homozygous for Fcgrttm1Dcr  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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.
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