NOD.Cg-Kit^W-41J Tyr ⁺ Prkdc^scid Il2rg^tm1Wjl/ThomJ

Stock number: 026622
Product name: NBSGW
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

NBSGW mice support engraftment of human hematopoietic stem cells without irradiation. They are suitable for use in applications related to xenotransplantation.

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

Detailed description

Xenograft NBSGW mice exhibit enhanced human hematopoietic chimerism in peripheral blood, bone marrow, and spleen when compared to non-irradiated engrafted NSG mice, with a level of chimerism similar to that seen in irradiated NSG mice. Chimerism in the peripheral blood of engrafted NBSGW mice was found to be 9-fold higher than chimerism exhibited by engrafted NSG mice. Serial transplantation of human hematopoietic stem cells is also supported with evidence of secondary graft expansion in the secondary recipients. Mice are mottled grey and white coat color due to the homozygous wildtype Tyr (tyrosinase) allele. While establishing the strain, mice that were homozygous for the wildtype Tyr (tyrosinase) allele were selected for further breeding to eliminate the albino coat color from the colony (allows easier visual phenotyping of Kit^W-41J allele). Mice that are homozygous for all three of these mutant alleles are viable and fertile.

These NBSGW mice may be expected to have a similar phenotype as the NSGW41 model (Stock No. 026497).

Development

Heterozygous C57BL/6J-Kit^W-41J/J (Stock No. 000119) mice were intercrossed to generate homozygotes. These homozygous C57BL/6J-Kit^W-41J/J mice were then crossed to NSG mice, NOD.Cg-Prkdc^scid Il2rg^tm1Wjl/SzJ (Stock No. 005557) to produce mice heterozygous for the following alleles: Kit^W-41J, Prkdc^scid, Il2rg^tm1Wjl, and the NOD/ShiLtJ Sirpa variant. The mice were intercrossed to homozygosity for all four alleles. The mice were then crossed to NOD.Cg-Prkdc^scid Il2rg^tm1Wjl/SzJ (Stock No. 005557) for 5 generations. Mice that were homozygous for the wildtype Tyr (tyrosinase) allele were selected for further breeding to eliminate the albino coat color from the colony (allows easier visual phenotyping of Kit^W-41J allele).

Allele

Symbol: Tyr⁺
Name: wild type
MGI accession ID: MGI:2432472
Generation method: Not Applicable
Marker symbol: Tyr
Marker name: tyrosinase
Chromosome: 7
Strain of origin: Not Applicable

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).