NOD.Cg-Prkdc^scid Il2rg^tm1Wjl Tg(IL6)1Sz/SzJ

Stock number: 028655
Product name: NSG+hIL6 , NSG hIL-6 , NSG huIL-6 , NSG.hIL-6 , NSG.huIL-6 , NSG-Hu-IL6
Strain synonyms: NSG huIL-6
Research areas: Cancer Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools, Virology Research

Description

NSG hIL-6 mice are NOD.scid.Il2Rγc^null ("NSG") animals expressing the human IL6 (interleukin 6) gene.

The NSG component involves two mutations on the NOD/ShiLtJ genetic background - severe combined immune deficiency (scid) and a complete null allele of the IL2 receptor common gamma chain (IL2rg^null). The scid mutation is in the DNA repair complex protein Prkdc and renders the mice B and T cell deficient. The IL2rg^null mutation prevents cytokine signaling through multiple receptors, leading to a deficiency in functional NK cells. The severe immunodeficiency allows the mice to be humanized by engraftment of human CD34+ hematopoietic stem cells (HSC), peripheral blood mononuclear cells (PBMC), patient derived xenografts (PDX), or adult stem cells and tissues. The immunodeficient NSG mice enable research in human immune function, infectious disease, diabetes, oncology, and stem cell biology.

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Detailed description

IL6 (interleukin 6) encodes a cytokine that functions in inflammation and the maturation of B cells. It is involved in multiple inflammation-associated disease states, including suspectibility to diabetes mellitus and systemic juvenile rheumatoid arthritis. Elevated levels of the encoded protein have been found in virus infections, including COVID-19 (disease caused by SARS-CoV-2).

NSG hIL-6 mice are NOD.scid.Il2Rγc^null ("NSG") animals expressing the human IL6 (interleukin 6) gene. Mice homozygous for scid, hemizygous/homozygous for the X-linked Il2rg knockout and hemizygous for the IL6 transgene are viable. The donating investigator has not attempt to make the transgene homozygous.

The NOD.Cg-Prkdc^scid Il2rg^tm1Wjl/SzJ mice, most often known by their branded name, NOD scid gamma (NSG™), do not express the Prkdc gene nor the X-linked Il2rg gene. NSG mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Histological examination of lymphoid tissues reveals absence of lymphoid cells and some cystic structures in the thymus, an absence of follicles in the spleen and markedly diminished celluarity of lymph nodes. NSG mice are deficient in mature lymphocytes, serum Ig is not detectable and natural killer (NK) cell cytotoxic activity is extremely low. These mice are resistant to lymphoma development even after sublethal irradiation treatment. These mutant mice have been shown to readily support engraftment of human CD34⁺ hematopoietic stem cells and represent a superior, long-lived model suitable for studies employing xenotransplantation strategies. NSG mice are highly sensitive to the diabetogenic effects of streptozotocin (STZ). The NSG-STZ preclinical model for pancreatic islet transplantation is now available from JAX® Services. Please note that the NSG carries the true null interleukin-2 receptor gamma chain mutation and should not be confused with other strains that express a truncated interleukin-2 receptor gamma chain as described in: "Modulation of hematopoiesis in mice with a truncated mutant of the interleukin-2 receptor gamma chain" Ohbo K et al. Blood 1996. 87:956-67.

Development

A transgenic construct containing the human interleukin 6, IL6, from the 161 Kb BAC clone RP11-469J8 was microinjected into the pronuclei of fertilized NOD.CB17-Prkdc^scid/J eggs. Founder line 1 was established and mated to to NOD.Cg-Prkdc^scid Il2rg^tm1Wjl/J (Stock No. 005557) mice, and progeny were interbred until all offspring were homozygous for scid, hemizygous/homozygous for the Il2rg targeted mutation and hemizygous for the transgene.

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: Tg(IL6)1Sz
Name: transgene insertion 1, Leonard Shultz
MGI accession ID: MGI:7539555
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Synonyms: huIL6
Marker symbol: Tg(IL6)1Sz
Marker name: transgene insertion 1, Leonard Shultz
Chromosome: UN
Strain of origin: NOD.Cg-Prkdc^scid/J
Molecular note: The transgenic construct contains the human interleukin 6 gene from the 161 Kb BAC clone RP11-469J8.