NOD.Cg-Prkdc^scid Il2rg^tm1Wjl Tg(PGK1-KITLG*220)441Daw/SzJ

Stock number: 017830
Product name: NSG-Tg(hu-mSCF)
Research areas: Cancer Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools, Virology Research

Description

These NSG-Tg(hu-mSCF) mice provide a supportive microenvironment that is conducive to engraftment of human hematopoietic stem cells and would be useful in studies of human mast cell development and allergic responses.

Detailed description

These mice express a 220 amino acid isoform of the human membrane-bound stem cell factor (hSCF or KITLG) in combination with the severe combined immunodeficiency allele (scid) of the protein kinase, DNA activated, catalytic polypeptide (Prkdc) gene and the Il2rg^tm1Wjl mutation of the interleukin 2 receptor, gamma chain gene. Newborn NSG-Tg(hu-mSCF) mice engraft human hematopoietic stem cells without pre-conditioning irradiation treatment and develop mature functional humanized immune systems, capable of rejecting histoincompatible human skin grafts. Differentiated c-Kit⁺ human mast cells can be detected in bone marrow, spleen, and mucosal lung, gastric, and intestinal tissues of engrafted mutant mice.

Development

A transgenic construct containing the human stem cell factor (hSCF or KIT ligand, KITLG) cDNA encoding the 220 amino acid isoform under the control of the the human phosphoglycerate kinase 1 (PGK1) promoter, and splice donor/splice acceptor sequences, was microinjected into the pronuclei of fertilized C3H/HeJ eggs. Founder line 441 was subsequently established. Mice hemizygous for the transgene were crossed to NOD.Cg-Prkdc^scid mice (Stock No. 001303) for 10 generations. The mice were then crossed to NOD.Cg-Prkdc^scid Il2rg^tm1Wjl mice (Stock No. 005557), and bred to homozygosity for all the transgene/alleles (males are hemizygous for the X-linked Il2rg^tm1Wjl targeted mutation).

Allele

Symbol: Tg(PGK1-KITLG*220)441Daw
Name: transgene insertion 441, David A Williams
MGI accession ID: MGI:3817558
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(PGK1-KITLG*220)441Daw
Marker name: transgene insertion 441, David A Williams
Chromosome: UN
Strain of origin: C3H/HeJ
Expressed genes: KITLG,KIT ligand,human
Molecular note: A 1.3 kb fragment containing a minigene with the human PGK1 promoter, splice donor/splice acceptor (SD/SA) sequence, a human stem cell factor (hSCF or KITLG) cDNA encoding the 220 amino acid isoform, and a polyA sequence was injected into the pronuclei of fertilized C3H/HeJ eggs.

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.