These scid FcRn-/- hFcRn (32) Tg mice express a human alpha chain FCGRT molecule in lieu of the endogenous mouse Fcgrt. The scid allele makes the mice immunodeficient, therefore allowing the ability to test potential immunogenic hIgGs and to perform xenograft studies in addition to evaluating the pharmocokinetics of human immunoglobulin and Fc-domain based therapeutics.
Need assistance evaluating antibodies in FcRn mice? Human preclinical pharmacokinetic (PK) analysis is available. See our FcRn full service platform.
Dr. Derry Roopenian, The Jackson Laboratory
|Allele Type||Gene Symbol||Gene Name|
|Spontaneous||Prkdc||protein kinase, DNA activated, catalytic polypeptide|
|Allele Type||Gene Symbol||Gene Name|
|Targeted (Null/Knockout)||Fcgrt||Fc receptor, IgG, alpha chain transporter|
|Transgenic (Inserted expressed sequence, Humanized sequence)|
These mFcRn-/- hFcRn (32) Tg mice are homozygous for the knockout mutation of the FcRn α-chain (Fcgrttm1Dcr) and express a human FcRn α-chain (FCGRT) transgene. By itself, the homozygous Fcgrt KO allele mice have low serum levels of IgG and albumin (Roopenian et al. J Immunol. 2003 Apr 1;170(7):3528-33; Chadhury et al. J Exp Med. 2003 Feb 3;197(3):315-22; Stein et al. 2012).
They fail to recycle IgG and albumin, and to transport IgG across the neonatal gut. By introducing the FCGRT transgene the albumin levels are restored to wild type, but the IgG levels remain low due to species-specific binding of IgG by human FCGRT. The transgenic founder line 32 provides a model to study serum half-life of human IgG (hIgG), with a good correlation to cynomolgus monkey and human. In addition, the model may be used to compare the serum half-life of antibodies as when screening FcRn binding variants (Petkova et al. 2006). When comparing the Tg32 model to Tg276 (see Stock No. 004919) overall longer half-lives have been observed, making it a better model for short-lived hIGs and Fc-fusion proteins. The humanized FcRn-/- hFcRn (32) Tg mice that are also homozygous for the Prkdcscid allele produce no mature T cells or B cells, therefore allowing the ability to test potential immunogenic hIgGs and to perform xenograft studies in addition to
evaluating the pharmocokinetics of human immunoglobulin and Fc-domain based therapeutics.
These knockout/transgenic mice were generated in the laboratory of Dr. Derry Roopenian (The Jackson Laboratory) by crossing B6.Cg-Fcgrttm1Dcr Tg(FCGRT)32Dcr/DcrJ mice (STOCK No. 014565) to B6.Cg-Fcgrttm1Dcr Prkdcscid.
To generate the FcRn α-chain knockout mice (Fcgrttm1Dcr; 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-Neor 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 32 transgenic mice, a 33-Kb cosmid clone including the complete FCGRT gene (approximately 11kb as well as 10kb of 5' and 3' flanking sequences) was microinjected into fertilized C57BL/6J mouse eggs (Roopenian et al Methods Mol Biol. 2010;602:93-104).
Prkdcscid 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-Prkdcscid/Prkdcscid and C57BL/6J followed by sequential backcrossing of heterozygous animals of the F1 and male heterozygotes (identified by testcrossing) of subsequent generations to C57BL/6J. At the 10th backcross generation the mutation was made homozygous by brother-sister inbreeding.
|Expressed Gene||FCGRT, Fc fragment of IgG receptor and transporter, human|
|Site of Expression|
|Allele Name||severe combined immunodeficiency|
|Allele Synonym(s)||Prkdcscid; severe combined immunodeficiency|
|Gene Symbol and Name||Prkdc, protein kinase, DNA activated, catalytic polypeptide|
|Gene Synonym(s)||AI326420; DNA-PK; DNA-PKcs; DNAPDcs; DNPK1; DOXNPH; doxorubicin nephropathy; DNAPK; expressed sequence AU019811; dxnph; dxnph; scid; IMD26; HYRC; HYRC1; p350; slip; XRCC7; severe combined immunodeficiency; expressed sequence AI326420; AU019811; DNA-PKC; DNAPKc|
|Site of Expression||T and B lymphocytes.|
|Strain of Origin||C.B-17|
|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.|
|Allele Name||targeted mutation 1, Derry C Roopenian|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||targeted mutation 1, Derry C Roopenian; Fcgrttm1Dcr|
|Gene Symbol and Name||Fcgrt, Fc receptor, IgG, alpha chain transporter|
|Gene Synonym(s)||alpha-chain; FCRN; neonatal Fc receptor; FcRn|
|Strain of Origin||129X1/SvJ|
|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 32, Derry C Roopenian|
|Allele Type||Transgenic (Inserted expressed sequence, Humanized sequence)|
|Allele Synonym(s)||Tg(FCGRT)32Dcr; transgene insertion 32, Derry C Roopenian|
|Gene Symbol and Name||Tg(FCGRT)32Dcr, transgene insertion 32, Derry C Roopenian|
|Promoter||FCGRT, Fc fragment of IgG receptor and transporter, human|
|Expressed Gene||FCGRT, Fc fragment of IgG receptor and transporter, human|
|Strain of Origin||C57BL/6J|
|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. The resulting cosmid was microinjected into fertilized C57BL/6J mouse eggs. Founder line 32 was established. Transgene insertion occurred on Chr 2.|
When maintaining a live colony, mice homozygous for the FcRn ?-chain targeted allele (Fcgrttm1Dcr), homozygous for the scid allele, and hemizygous or homozygous for the hFcRn (32) transgene (Tg(FCGRT)32Dcr) may be bred together.
When using the scid FcRn-/- hFcRn (32) Tg mouse strain in a publication, please cite the originating article(s) and include JAX stock #018441 in your Materials and Methods section.
|Homozygous for Fcgrt<tm1Dcr>, Homozygous for Prkdc<scid> , Homozygous for Tg(FCGRT)32Dcr|
We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.
|Frozen Mouse Embryo||$2,595.00 per straw or vial|
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