NOD.Cg-Kit^W-41J Prkdc^scid Il2rg^tm1Wjl/WaskJ

Stock number: 026497
Product name: NSGW41
Research areas: Cancer Research, Dermatology Research, Developmental Biology Research, Endocrine Deficiency Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Mouse/Human Gene Homologs, Neurobiology Research, Reproductive Biology Research, Research Tools, Sensorineural Research, Virology Research

Description

We are currently not distributing this stock due to legal restraints.

Alternative Option: Stock No. 026622 NOD.Cg-Kit^W-41J Tyr⁺ Prkdc^scid Il2rg^tm1Wjl/ThomJ (NBSGW)

Stock No. 026497: NSGW41 mice (NSG Kit^W41/W41) support long-term engraftment of human hematopoietic stem cells without irradiation. They are suitable for use in applications related to xenotransplantation.

Detailed description

NSGW41 mice are NOD.scid.Il2Rγc^null ("NSG"; Stock No. 005557) animals also harboring the spontaneous Kit^W-41J allele. Mice homozygous for all 3 alleles are viable and fertile (males would be hemizygous for the X-linked Il2rg allele). Loss of endogenous Kit function, conferred by the Kit^W-41J allele, impairs endogenous mouse hematopoietic stem cells, allowing engraftment of human hematopoietic stem cells without irradiation. These mice support improved human erythropoiesis up to the normoblast stage and platelet formation as compared to irradiated NSG recipients. Colony formation of engrafted of human CD45+ cells into bone marrow of NSGW41 mice is approximately 2 times more than the number of colonies formed in bone marrow from control irradiated NSG mice.

These NSGW41 mice may be expected to have a similar phenotype as the NBSGW model (Stock No. 026622) that also carries the wildtype Tyr allele. Although viable and fertile, homozygous NSGW41 mice are immunodeficient: they have no mature T cells or B cells, lack functional natural killer (NK) cells, develop a macrocytic anemia and are deficient in cytokine signaling.

Development

NSGW41 mice are NOD.scid.Il2Rγc^null ("NSG") animals with the Kit^W-41J allele. NSGW41 mice harbor several mutations, as 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 spontaneous Kit^W-41J allele arose on the C57BL/6J background and contains a missense point mutation (G to A) at nucleotide 2519, within the kinase domain, that results in a valine to methionine substitution at amino acid 831. C57BL/6J-Kit^W-41J/J mice are available from The Jackson Laboratory Repository as Stock No. 000119.

Dr. Claudia Waskow obtained mice carrying the Kit^W-41J allele from Dr. Norman Iscove (who obtained C57BL/6J-Kit^W-41J/J mice from The Jackson Laboratory), and crossed the mice to NSG mice, NOD.Cg-Prkdc^scid Il2rg^tm1Wjl/SzJ (Stock No. 005557). After 5 generations of crossing to NSG mice (Stock No. 005557), the mice were sequenced to confirm presence of the NOD Sirpa and CD45.1 variants. After 16 generations of crossing to NSG mice (Stock No. 005557), the mice were bred to homozygosity for all 3 alleles (males would be hemizygous for the X-linked Il2rg allele), and the NOD Sirpa (CD45.1) allele variant. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize NSG, NOD.Cg-Prkdc^scid Il2rg^tm1Wjl/SzJ oocytes (Stock No. 005557).

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.

Allele

Symbol: Kit^W-41J
Name: dominant spotting 41 Jackson
MGI accession ID: MGI:1856244
Generation method: Spontaneous
Marker symbol: Kit
Marker name: KIT proto-oncogene receptor tyrosine kinase
Chromosome: 5
Strain of origin: C57BL/6J
Molecular note: Comparison of the coding sequence of this allele with normal c-kit indicated a G-to-A point mutation in the kinase domain at nucleotide 2519 that results in a valine to methionine substitution at amino acid 831 (p.V831M).