NOD.Cg-Prkdc^scid Il2rg^tm1Wjl Tg(CMV-IL3,CSF2,KITLG)1Eav/MloySzJ

Stock number: 013062
Product name: NSG-SGM3
Strain synonyms: NSGS, NSG-SGM3, NOD-scid IL2Rgnull-3/GM/SF, NSG-Triples [NSG-T]
Research areas: Cancer Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools, Virology Research

Description

The triple transgenic NSG-SGM3 (NSGS) mice expressing human IL3, GM-CSF (CSF2) and SCF (KITLG) combine the features of the highly immunodeficient NOD scid gamma (NSG) mouse with cytokines that support the stable engraftment of myeloid lineages and regulatory T cell populations. As a result, these NSG-SGM3 mice allow superior engraftment of diverse hematopoietic lineages and primary AML samples than other models and are useful for immuno-oncology, immunology and infectious disease studies.

To order this model with CD34+ or PBMC engraftment, please visit our Humanized Mice page.

Detailed description

The triple transgenic NSG-SGM3 (NSGS) mice are NOD.scid.Il2Rγc^null ("NSG") animals with the SGM3 coinjected transgenes, each with a human cytomegalovirus promoter/enhancer sequence driving expression of the human interleukin-3 gene (IL3; IL-3), the human granulocyte/macrophage-stimulating factor gene (CSF2; GM-CSF), or the human Steel factor gene (KITLG; SCF or SF).

NSG-SGM3 mice combine the features of the highly immunodeficient NSG mouse with cytokines (IL3, GM-CSF and SCF) that support the stable engraftment of myeloid lineages and regulatory T cell populations. NSG-SGM3 mice allow superior engraftment of diverse hematopoietic lineages and primary AML samples than other models and are useful for immuno-oncology, immunology and infectious disease studies.

These NSG-SGM3 mice constitutively produce 2-4 ng/ml serum levels of human IL-3, GM-CSF, and SF.

Similar to other immunodeficient strains, maintaining NSG-SGM3 mice in high health status (specific pathogen-free) vivaria promotes overall colony health. If homozygous NSG-SGM3 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, flow cytometry data and categorized, up-to-date references.

Development

Three separate transgenes were designed each carrying either the human interleukin-3 gene (IL3; IL-3), the human granulocyte/macrophage-stimulating factor gene (CSF2; GM-CSF), or the human Steel factor gene (KITLG; SCF or SF). Expression of each gene is driven by a human cytomegalovirus promoter/enhancer sequence, and is followed by a human growth hormone cassette and a polyadenylation (polyA) sequence. The transgenes were microinjected into fertilized C57BL/6xC3H/HeN oocytes. The resulting founders, carrying all three transgenes (3GS) were backcrossed to BALB/c-scid/scid mice for several generations and subsequently backcrossed to NOD.CB17-Prkdc^scid mice for at least 11 generations. These mice were bred to NOD.Cg-Prkdc^scid Il2rg^tm1Wjl mice, and were then interbred until all offspring were homozygous for 3GS and the IL2rg targeted mutation. Upon arrival at The Jackson Laboratory, transgenic mice were bred to NOD.Cg-Prkdc^scid Il2rg^tm1Wjl/SzJ mice (Stock No. 005557) for one generation to establish the colony. Thereafter, females homozygous for Prkdc^scid, homozygous for Il2rg^tm1Wjl and homozygous for the 3GS transgenes were bred with males homozygous for Prkdc^scid, hemizygous for the X-linked Il2rg^tm1Wjl and homozygous for the 3GS transgenes.

Allele

Symbol: Tg(CMV-IL3,CSF2,KITLG)1Eav
Name: transgene insertion 1, CJ Eaves
MGI accession ID: MGI:3653745
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(CMV-IL3,CSF2,KITLG)1Eav
Marker name: transgene insertion 1, CJ Eaves
Chromosome: UN
Strain of origin: (C57BL/6 x C3H/HeN)F1
Expressed genes: IL3,interleukin 3,human; CSF2,colony stimulating factor 2,human; KITLG,KIT ligand,human
Molecular note: cDNAs encoding human interleukin 3, colony stimulating factor 2 (granulocyte-macrophage) and kit ligand were independently ligated into expression cassettes in which the cDNA resides downstream of the cytomegalovirus (CMV) promoter/enhancer sequence and is followed by human growth factor intronic and polyadenylation sequences. A transgenic mouse that was shown by ELISA to have serum levels of all three growth factors at ng/ml levels was used to establish a line with the same phenotype.

Allele

Symbol: Prkdc^scid
Name: severe combined immunodeficiency
MGI accession ID: MGI:1857113
Generation method: Spontaneous
Marker symbol: Prkdc
Marker name: protein kinase, DNA activated, catalytic polypeptide
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
Marker symbol: Il2rg
Marker name: interleukin 2 receptor, gamma chain
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.