NOD.Cg-Rag1^tm1Mom Kit^W-41J Il2rg^tm1Wjl/EavJ

Stock number: 026014
Strain synonyms: NRG-W41
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

Description

These NRG-W41 mice support engraftment of human hematopoietic stem cells with or without sub-lethal irradiation. They are suitable for use in applications related to xenotransplantation.

Detailed description

NRG-W41 mice are homozygous for Kit^W-41J Rag1^tm1Mom Il2rg^tm1Wjl and the NOD/ShiLtJ Sirpa variant (males would be hemizygous for the X-linked Il2rg^tm1Wjl), and are viable and fertile.

Following low dose irradiation (150 cGy) and 20 weeks post-transplantation, repopulated bone marrow cells and spleen NRG-W41 mice can achieve higher levels of human CD45+ cells, compared to NRG mice.

Human hematopoietic cell types detected include erythrocytes and platelets. These mice do not carry the Prkdc^scid allele which increases sensitivity to ionizing radiation.

Development

Heterozygous C57BL/6J-Kit^W-41J/J (Stock No. 000119) mice were crossed to NRG, NOD.Cg-Rag1^tm1Mom Il2rg^tm1Wjl/SzJ, mice (Stock No. 007799), and the resulting mice were crossed to NRG mice for 8 generations with selection for Kit^W-41J to produce

mice heterozygous for Kit^W-41J, female homozygous (or male hemizygous) for Il2rg^tm1Wjl, and homozygous for Rag1^tm1Mom and the NOD/ShiLtJ Sirpa variant.

Upon arrival, sperm was cryopreserved.

Allele

Symbol: Rag1^tm1Mom
Name: targeted mutation 1, Peter Mombaerts
MGI accession ID: MGI:1857241
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Rag1
Marker name: recombination activating gene 1
Chromosome: 2
Strain of origin: 129S7/SvEvBrd-Hprt1⁺
Site of expression: expression is seen in bone marrow derived cell lines.
Molecular note: A 1356 bp genomic fragment of the Rag1 gene, encoding the nuclear localization signal and the zinc-finger motif, was replaced by a neomycin cassette. A mutant transcript expressed from this allele was detected by Northern blot in bone marrow derived cell lines from homozygous mice.

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).