B6.Cg-Tg(ALB)9463J Tg(FCGRT)32Dcr Alb^em12Mvw Fcgrt^tm1Dcr/J

Stock number: 037524
Product name: Tg32 hALB , HuPK™
Strain synonyms: FcRn-/- hFcRn (32) Tg; Alb KO; hALB (9463) Tg
Research areas: Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

This Tg32 hAlb-BAC mouse model expresses a human Fc gamma receptor and transporter (FCGRT) and a human albumin (ALB) transgene, each driven by their own native promoters. Tg32 hAlb-BAC mice also carry Alb knock-out and Fcgrt knock-out alleles, resulting in ablation of endogenous Alb and Fcgrt expression. These mice may be useful for studying the pharmacokinetics (PK) and pharmacodynamics (PD) of human albumin therapeutics as well as human immunoglobulin G (IgG) and Fc-domain based therapeutics.

Need assistance evaluating antibodies in FcRn mice? Human preclinical pharmacokinetic (HuPK™) analysis is available. See our HuPK full service platform.

Detailed description

Tg32 hAlb-BAC mice harbor a human Fc gamma receptor and transporter (FCGRT) transgene, under control of its own native promoter, as well as a human albumin (ALB) transgene. These mice also harbor Alb knock-out (KO) and Fcgrt KO alleles, resulting in ablation of endogenous Alb and Fcgrt expression.

Mice that are homozygous for all alleles are viable with no overt phenotype. It is recommended that mice hemizygous for Tg(ALB)9463J, homozygous for Tg(FCGRT)32Dcr, heterozygous for Alb^em12Mvw, and homozygous Fcgrt^tm1Dcr are mated with mice that are non-carrier for Tg(ALB)9463J, homozygous for Tg(FCGRT)32Dcr, homozygous for Alb^em12Mvw, and homozygous Fcgrt^tm1Dcr. Experience at The Jackson Laboratory indicates mating homozygous x homozygous for the Alb^em12Mvw allele tends to be non-productive.

Initial validation data indicates that Tg32 hAlb-BAC mice express physiological levels of human serum albumin (HSA) at 25 to 40mg/ml. This Tg32 hAlb-BAC mouse model is a preclinical tool that generates translational Pharmacokinetic (PK) data for albumin-based drugs and provides Pharmacodynamic (PD) data for FcRn inhibitors.

Need assistance evaluating antibodies in FcRn mice? Human preclinical pharmacokinetic (PK) analysis is available. See our FcRn full service platform.

Development

To create the human ALB (hALB) transgene, an ~120 kb BAC construct was obtained originally containing the entire human albumin (ALB) gene as well as ~45.9 kb upstream sequences (including the ENSG00000302431 region) and ~56.9 kb downstream sequences (including the AFP gene). This BAC was linearized and microinjected into fertilized FcRn-/- hFcRn(32)Tg (Stock No. 014565) oocytes. Offspring from founder line 9463 were bred to FcRn-/- hFcRn(32)Tg; Alb knock-out (KO) (Stock No. 025201) mice. The Tg(ALB)9463J transgene was found to have integrated on Chromosome 2 ~159 Mb (mouse genome mm10) as a single intact copy (with possible tandem insertion of a truncated BAC missing its ~25 kb region from the last AFP exon and downstream). The mouse genomic region between the insertion breakpoints is deleted. There are no annotated genes within the deleted mouse region nor at the integration breakpoints [June 2025]. The Tg32 hAlb-BAC mice provided as the Stock No. 037524 founder animals were determined to have medium expression levels of the hALB transgene.

Stock No. 025201 FcRn-/- hFcRn(32)Tg; Alb knock-out (KO) mice have a TALEN-generated deletion of the mouse albumin gene (Alb) on Chromosome 5, a knock-out mutation for the mouse Fc receptor, IgG, alpha chain transporter gene (Fcgrt) on Chromosome 7 and a transgene expressing the human FCGRT gene under the control of its own native promoter (hTg32) on Chromosome 2 (101,081,712-101,081,713; mouse genome mm10). See Stock No. 014565 for more information on Tg(FCGRT)32Dcr transgene copy number and other human genes in this transgene.

Allele

Symbol: Alb^em12Mvw
Name: endonuclease-mediated mutation 12, Michael Wiles
MGI accession ID: MGI:5494605
Generation method: Endonuclease-mediated
Attributes: Null/Knockout
Marker symbol: Alb
Marker name: albumin
Marker synonyms: Alb1; Alb-1; Albza; FDAHT; HSA; PRO0883; PRO0903; PRO1341
Chromosome: 5
Strain of origin: B6.Cg-Fcgrt^tm1Dcr Tg(FCGRT)32Dcr/DcrJ
Molecular note: Exon 4 was targeted by introduction of TALEN mRNA into fertilized B6.Cg-Fcgrt^tm1Dcr 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.

Allele

Symbol: Fcgrt^tm1Dcr
Name: targeted mutation 1, Derry C Roopenian
MGI accession ID: MGI:3511510
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: FcRn^-
Marker symbol: Fcgrt
Marker name: Fc receptor, IgG, alpha chain transporter
Marker synonyms: alpha-chain; FcgammaRn; FCRN; neonatal Fc receptor
Chromosome: 7
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

Symbol: Tg(FCGRT)32Dcr
Name: transgene insertion 32, Derry C Roopenian
MGI accession ID: MGI:4944199
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Synonyms: hFcRn(32) vhFcRn (32) Tg hFcRn (32) Tg; Tg32
Marker symbol: Tg(FCGRT)32Dcr
Marker name: transgene insertion 32, Derry C Roopenian
Chromosome: 2
Strain of origin: C57BL/6J
Expressed genes: FCGRT,Fc fragment of IgG receptor and transporter,human
Site of expression: The transgene expresses human FCGRT from the native human promoter, and displays a physiological human FCGRT expression pattern (Latvala et al., 2017).
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

Symbol: Tg(ALB)9463J
Name: transgene insertion 9463, Jackson Laboratory
MGI accession ID: MGI:7716597
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(ALB)9463J
Marker name: transgene insertion 9463, Jackson Laboratory
Chromosome: 2
Strain of origin: B6.Cg-Fcgrt^tm1Dcr Tg(FCGRT)32Dcr/DcrJ
Molecular note: An ~120 kb BAC construct was containing the entire human albumin (ALB) gene as well as ~45.9 kb upstream sequences (including the ENSG00000302431 region) and ~56.9 kb downstream sequences (including the AFP gene).was linearized and microinjected into fertilized B6.Cg-Fcgrt^tm1Dcr Tg(FCGRT)32Dcr/DcrJ. Offspring from founder line 9463 was established. The transgene was found to have integrated as a single copy into chromosome 2 (15869581-159382454).