FcRn-/- hFcRn line 32 Tg mice are useful in evaluating the pharmacokinetics and pharmacodynamics of human immunoglobulin G. These mice carry a null mutation for the mouse gene and a transgene expressing the human FcRn α-chain transgene under the control of its natural human promoter.
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
FcRn-/- hFcRn (32) Tg mice harbor a knockout allele of the FcRn α-chain (Fcgrttm1Dcr) and express a human FcRn α-chain (FCGRT) transgene under control of the human FcRn promoter. In this line, serum albumin levels are slightly above those seen in C57BL/6J mice, while mouse IgG levels are low due to the species-specific activity of human FcRn. Line 32 is more efficient in prolonging the serum half-life of hIgG compared with line 276 (see Stock no. 004919). In Petkova et. al. 2006, the antibody half-life of Hu4D5-IgG1 antibodies in hemizygous hFcRn (32) Tg/0 mice of this strain is shown to be similar to that observed in FcRn-/- hFcRn (276) Tg/Tg homozygous mice (see Stock no. 004919). (Hu4D5-IgG1 human antibodies are directed against human EGFR2.) Mice hemizygous or homozygous for the hFcRn (32) Tg in this model may be useful for studying human FcRn biology and the behavior of IgG antibodies and Fc-domain proteins, including Fc-engineered molecules.
These knockout/transgenic mice were generated in the laboratory of Dr. Derry Roopenian (The Jackson Laboratory) by crossing Fcgrttm1Dcr mutant mice with Tg(FCGRT)32Dcr transgenic mice (coisogenic on a C57BL/6J genetic background). These double mutant mice were backcrossed for 11 generations to C57BL/6J prior to transfer to The Jackson Laboratory Repository.
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.
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.
|Expressed Gene||FCGRT, Fc fragment of IgG receptor and transporter, human|
|Site of Expression|
|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 Fcgrttm1Dcr allele and homozygous for the Tg(FCGRT)32Dcr transgene can be bred together.
When using the FcRn-/- hFcRn (32) Tg mouse strain in a publication, please cite the originating article(s) and include JAX stock #014565 in your Materials and Methods section.
|Homzygous for Fcgrt<tm1Dcr> and homozygous for Tg(FCGRT)32Dcr, 1 pair minimum|
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.
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