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 Prkdcscid 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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Dr. Derry Roopenian, The Jackson Laboratory
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Spontaneous | Prkdc | protein kinase, DNA activated, catalytic polypeptide |
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Fcgrt | Fc receptor, IgG, alpha chain transporter |
Allele Type |
---|
Transgenic (Inserted expressed sequence, Humanized sequence) |
These mice are homozygous for a FcRn alpha-chain knockout allele (Fcgrttm1Dcr), the Prkdcscid 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.
These knockout/transgenic mice were generated in the laboratory of Dr. Derry Roopenian (The Jackson Laboratory) by crossing B6.Cg-Fcgrttm1Dcr Tg(CAG-FCGRT)279Dcr/DcrJ mice (Stock No. 004919) to B6.Cg-Fcgrttm1Dcr Prkdcscid/DcrJ (Stock No. 018541).
To generate the FcRn alpha-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 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 Fcgrttm1Dcr allele (B6.Cg-Fcgrttm1Dcr Tg(CAG-FCGRT)279Dcr/DcrJ, see also Stock No. 004919).
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 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).
Expressed Gene | FCGRT, Fc fragment of IgG receptor and transporter, human |
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Site of Expression |
Allele Name | severe combined immunodeficiency |
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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-Ighb/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*). |
Allele Name | targeted mutation 1, Derry C Roopenian |
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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. |
Allele Name | transgene insertion 276, Derry C Roopenian |
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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. |
When maintaining a live colony, these mice can be bred as homozygotes for the Fcgrttm1Dcr and Prkdcscid alleles and the Tg(CAG-FCGRT)279Dcr transgene.
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.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous for Fcgrt<tm1Dcr, Heterozygous for Prkdc<scid>, Hemizygous for Tg(CAG-FCGRT)276Dcr, |
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 |
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