This TALEN-mediated deletion in Alb results in the absence of any albumin protein in the blood. When combined with the knockout allele of the FcRn a-chain and a transgene expressing a human FcRn a-chain (FCGRT) under control of the human FcRn promoter, this albumin-deficient model may be useful for studying human serum albumin pharmacokinetics.
Need assistance evaluating antibodies in FcRn mice? Human preclinical pharmacokinetic (PK) analysis is available. See our FcRn full service platform.
Michael Wiles, The Jackson Laboratory
Genetic Background | Generation |
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N1F4+F11
|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Fcgrt | Fc receptor, IgG, alpha chain transporter |
Allele Type |
---|
Transgenic (Inserted expressed sequence, Humanized sequence) |
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Endonuclease-mediated (Null/Knockout) | Alb | albumin |
Starting at:
$425.00 Domestic price for female 4-week |
550.00 Domestic price for breeder pair |
Mice homozygous for the Albem12Mvw allele lack albumin protein in their blood. FcRn-/- hFcRn (32) Tg mice harbor a knockout allele of the Fc receptor, IgG, alpha chain transporter (Fcgrttm1Dcr) and express a human FcRn a-chain (FCGRT) transgene under control of the human FcRn promoter. Mouse IgG levels are low due to the species-specific activity of human FcRn. Mice do not exhibit any gross abnormal phenotype. This albumin-deficient model may be useful for studying the biology and pathobiology of serum albumin as well as evaluating human albumin pharmacokinetics.
C57BL/6J-Albem8Mvw/MvwJ (Stock No. 025200) was generated as a control for this strain.
A targeting scheme was designed using a TALEN-mediated Non-Homologous End Joining (NHEJ) repair pathway to knock out the mouse albumin gene in B6.Cg-Fcgrttm1Dcr Tg(FCGRT)32Dcr/DcrJ ((Stock No. 014565)). TALEN mRNAs were introduced into mutant zygotes, and the resulting founder mouse (#6074) was crossed to a B6.Cg-Fcgrttm1Dcr Tg(FCGRT)32Dcr/DcrJ mouse in order to characterize the mutation, a 2-base deletion resulting in early termination of the translated protein. N1 Heterozygous offspring were filial-crossed to establish the colony as homozygotes.
Expressed Gene | FCGRT, Fc fragment of IgG receptor and transporter, human |
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Site of Expression | |
Site of Expression |
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 32, Derry C Roopenian |
---|---|
Allele Type | Transgenic (Inserted expressed sequence, Humanized sequence) |
Allele Synonym(s) | hFcRn(32) vhFcRn (32) Tg hFcRn (32) Tg; Tg32 |
Gene Symbol and Name | Tg(FCGRT)32Dcr, transgene insertion 32, 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 | C57BL/6J |
Chromosome | 2 |
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. |
Allele Name | endonuclease-mediated mutation 12, Michael Wiles |
---|---|
Allele Type | Endonuclease-mediated (Null/Knockout) |
Allele Synonym(s) | |
Gene Symbol and Name | Alb, albumin |
Gene Synonym(s) | |
Strain of Origin | B6.Cg-Fcgrttm1Dcr Tg(FCGRT)32Dcr/DcrJ |
Chromosome | 5 |
Molecular Note | Exon 4 was targeted by introduction of TALEN mRNA into fertilized B6.Cg-Fcgrttm1Dcr Tg(FCGRT)32Dcr/DcrJ oocytes and the resulting founder screened and found to have a 2 base pair deletion beginning at Chromosome 5 base 90,464,113 (GRCm38.p2) which is predicted to result in a frame shift then a premature stop codon 5 amino acids downstream of the encoded frame shift. By ELISA, heterozgyotes have a decrease in serum albumin of approximately 30 percent and homozygotes have no detectable serum albumin. |
While maintaining a live colony, these mice are bred as homozygotes. Experience at The Jackson Laboratory indicates mating males and females homozygous for all 3 genes to be highly non-productive and litters produced often don't make it to wean. However, we have find that mating het, hom, hom x hom, hom, hom and reciprocal to consistantly provide litters. It is not uncommon to lose the first litter.
or
homozygous for Albem12Mvw, Homozygous for Fcgrttm1Dcr, Homozygous for Tg(FCGRT)32Dcr x Heterozygous for Albem12Mvw, Homozygous for Fcgrttm1Dcr, Homozygous for Tg(FCGRT)32Dc
When using the B6.Cg-Tg(FCGRT)32Dcr Albem12Mvw Fcgrttm1Dcr/MvwJ mouse strain in a publication, please cite the originating article(s) and include JAX stock #025201 in your Materials and Methods section.
Service/Product | Description | Price |
---|---|---|
Heterozygous and homozygous for Alb<em12Mvw>, Homzygous for Fcgrt<tm1Dcr> and Tg(FCGRT)32Dcr |
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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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