NOD.Cg-Fcgrt^tm1Dcr Prkdc^scid Il2rg^tm1Wjl Tg(FCGRT)32Dcr/J

Stock number: 028615
Product name: NSG FcRn-/- hFcRn (32) Tg , HuPK™
Research areas: Cancer Research, Cardiovascular Research, Developmental Biology Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools, Virology Research

Description

NSG FcRn-/- hFcRn (32) Tg mice are NOD.scid.Il2Rγc^null ("NSG") animals with a humanized FcRn α-chain (FcRn-/- hFcRn line 32 Tg). Homozygous NSG FcRn-/- hFcRn (32) Tg mice have no mature T cells or B cells, lack functional natural killer (NK) cells, are deficient in cytokine signaling, and express human FcRn in place of the endogenous mouse FcRn.

These mice may be useful in evaluating the pharmacokinetics/pharmacodynamics of human immunoglobulin G in transplantation studies, human tumor xenografts and mouse tumor allografts. For example, examining the ability of anti-FcRn to inhibit angiogenesis and other tumor/stroma interactions.
In addition to these NSG FcRn-/- hFcRn (32) Tg mice (Stock No. 028615), the NSG FcRn-/- animals are also available with the hFcRn (276) Tg as Stock No. 028616.

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

Detailed description

NSG FcRn-/- hFcRn (32) Tg mice are NOD.scid.Il2Rγc^null ("NSG") animals with a humanized FcRn α-chain (FcRn-/- hFcRn line 32 Tg).

NSG FcRn-/- hFcRn (32) Tg females homozygous for all three mutations and the transgene, and males homozygous for scid, homozygous for FcRn null, hemizygous for the X-linked Il2Rγc^null and homozygous for the hFcRn(32) transgene may be collectively referred to as homozygous NSG FcRn-/- hFcRn (32) Tg mice.

Although viable and fertile, homozygous NSG FcRn-/- hFcRn (32) Tg mice are immunodeficient: they have no mature T cells or B cells, lack functional natural killer (NK) cells and are deficient in cytokine signaling. They have endogenous FcRn α-chain expression deleted and replaced a human FcRn α-chain (FCGRT) transgene under control of its human FcRn promoter.


For additional information on the phenotype of FcRn-/- hFcRn (32) Tg mice, see Stock No. 014565.

Similar to other immunodeficient strains, maintaining homozygous NSG FcRn-/- hFcRn (32) Tg mice in high health status (specific pathogen-free) vivaria promotes overall colony health. If homozygous NSG FcRn-/- hFcRn (32) Tg animals are maintained in low health barrier rooms, the use of medicated water (e.g., sulfatrim/trimethoprim-sulfa or enrofloxacin/Baytril) is suggested to increase overall colony health.

View our Resources for the NSG mouse model, including discussion forum, immunodeficient model comparison, and categorized, up-to-date references.

Development

NSG FcRn-/- hFcRn (32) Tg mice are NOD.scid.Il2Rγc^null ("NSG") animals with the FcRn knock-out allele and the hFcRn (32) transgene expressing human FcRn α-chain. Each mutation/transgene are described below.

NSG mice are non-obese diabetic animals (NOD/ShiLtJ) harboring the spontaneous severe combined immunodeficiency mutation (Prkdc^scid) on chromosome 16 and the Il2Rγc^null mutation at ~101 Mbp on the X chromosome (Il2rg^tm1Wjl created by Dr. Warren J. Leonard [NIH]). NSG mice are described and available from The Jackson Laboratory Repository as Stock No. 005557.

The FcRn α-chain knock-out allele (Fcgrt^tm1Dcr) was generated in the laboratory of Dr. Derry Roopenian (The Jackson Laboratory), and is described for Stock No. 003982. Briefly, it has 1588 nucleotides (encoding promoter sequence 5' of the transcriptional start site, exon1, intron 2, and most of exon2) replaced with a PGK-Neo^r cassette.

The hFcRn (32) transgene (Tg(FCGRT)32Dcr) was generated in the laboratory of Dr. Derry Roopenian (The Jackson Laboratory), and is described for Stock No. 014565. The transgene is a 33 kb cosmid clone including the complete human ~11 kb FCGRT gene (as well as ~10 kb of 5' and 3' flanking sequences). Transgene insertion occurred on mouse Chromosome 2 (101,081,712-101,081,713; mouse genome mm10). See Stock No. 014565 for more information on transgene copy number and other human genes in this transgene.

In 2016, some C57BL/6J-congenic FcRn-/- hFcRn (32) Tg mice (from Stock No. 014565) were bred to NSG mice (from Stock No. 005557) for five generations. The resulting NSG FcRn-/- hFcRn (32) Tg mice were bred together for several generations, and then made available as Stock No. 028615. In November 2017, SNP analyses show the colony to be greater than 97% NOD.

Allele

Symbol: Prkdc^scid
Name: severe combined immunodeficiency
MGI accession ID: MGI:1857113
Generation method: Spontaneous
Synonyms: scid
Marker symbol: Prkdc
Marker name: protein kinase, DNA activated, catalytic polypeptide
Marker synonyms: DNAPDcs; DNAPK; DNA-PK; DNAPKc; DNA-PKC; DNA-PKcs; DNPK1; DOXNPH; dxnph; HYRC; HYRC1; IMD26; p350; S473K; slip; XRCC7
Chromosome: 16
Strain of origin: C.BKa-Igh^b/Icr
Site of expression: T and B lymphocytes.
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

Symbol: Il2rg^tm1Wjl
Name: targeted mutation 1, Warren J Leonard
MGI accession ID: MGI:1857455
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: [KO]gammac; CD132^-; gammac^-; gc^-; Il2rg^tm1Wjll; IL2Rgamma^null
Marker symbol: Il2rg
Marker name: interleukin 2 receptor, gamma chain
Marker synonyms: [g]c; Ab2-183; Cd132; CIDX; common cytokine receptor gamma chain; common gamma chain; gamma C receptor; gamma(c); gammaC; gc; IL-2RG; IMD4; P64; SCIDX; SCIDX1
Chromosome: X
Strain of origin: 129S4/SvJae
Site of expression: Primarily lymphoid cells.
Molecular note: A neomycin resistance cassette replaced part of exon 3 and all of exons 4 - 8 of the gene, resulting in the loss of most of the extracellular domain and all of the transmembrane and cytoplasmic domains of the protein.

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.