Overview

Also Known As:NSGW41

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.

Donating Investigator

Claudia Waskow, Dresden University of Technology

Genetic overview

Genetic Background	Generation

Kit^W-41J

Allele Type	Gene Symbol	Gene Name
Spontaneous	Kit	KIT proto-oncogene receptor tyrosine kinase

Prkdc^scid

Allele Type	Gene Symbol	Gene Name
Spontaneous	Prkdc	protein kinase, DNA activated, catalytic polypeptide

Il2rg^tm1Wjl

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Il2rg	interleukin 2 receptor, gamma chain

View Genetics

Research Applications

Research Tools
Internal/Organ Research
Immunology, Inflammation and Autoimmunity Research
Virology Research
Reproductive Biology Research
Cancer Research
Mouse/Human Gene Homologs
Endocrine Deficiency Research

View All Research Applications

Details

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).

Control Suggestions

Approximate Controls

005557 NOD.Cg-Prkdc^scid Il2rg^tm1Wjl/SzJ

Additional Information

Considerations for Choosing Controls

Selected References

Cosgun KN; Rahmig S; Mende N; Reinke S; Hauber I; Schafer C; Petzold A; Weisbach H; Heidkamp G; Purbojo A; Cesnjevar R; Platz A; Bornhauser M; Schmitz M; Dudziak D; Hauber J; Kirberg J; Waskow C. 2014. Kit regulates HSC engraftment across the human-mouse species barrier. Cell Stem Cell 15(2):227-38PubMed: 25017720 MGI: J:232320
Rahmig S; Kronstein-Wiedemann R; Fohgrub J; Kronstein N; Nevmerzhitskaya A; Bornhauser M; Gassmann M; Platz A; Ordemann R; Tonn T; Waskow C. 2016. Improved Human Erythropoiesis and Platelet Formation in Humanized NSGW41 Mice. Stem Cell Reports 7(4):591-601PubMed: 27618723 MGI: J:235122

View All References

Genetics

Kit^W-41J

Allele Symbol: Kit^W-41J

Allele Name	dominant spotting 41 Jackson
Allele Type	Spontaneous
Allele Synonym(s)	Kit^W41; W⁴¹; W-41
Gene Symbol and Name	Kit, KIT proto-oncogene receptor tyrosine kinase
Gene Synonym(s)
Strain of Origin	C57BL/6J
Chromosome	5
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).

Prkdc^scid

Allele Symbol: Prkdc^scid

Allele Name	severe combined immunodeficiency
Allele Type	Spontaneous
Allele Synonym(s)	SCID
Gene Symbol and Name	Prkdc, protein kinase, DNA activated, catalytic polypeptide
Gene Synonym(s)
Site of Expression	T and B lymphocytes.
Strain of Origin	C.BKa-Igh^b/Icr
Chromosome	16
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*).

Il2rg^tm1Wjl

Allele Symbol: Il2rg^tm1Wjl

Allele Name	targeted mutation 1, Warren J Leonard
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	[KO]gammac; CD132^-; gammac^-; gc^-; Il2rg^tm1Wjll; IL2Rgamma^null
Gene Symbol and Name	Il2rg, interleukin 2 receptor, gamma chain
Gene Synonym(s)
Site of Expression	Primarily lymphoid cells.
Strain of Origin	129S4/SvJae
Chromosome	X
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.
Mutations Made By	Dr. Warren Leonard, NHLBI, NIH

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Prkdc^scid related

Research Tools
- Toxicology Research
  - xenograft/transplant host
- Cancer Research
  - B and T cell deficiency, xenograft/transplant host
Internal/Organ Research
- Lymphoid Tissue Defects
  - B and T cell deficiency
Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - B and T cell deficiency
Virology Research
- B and T Cell Deficiency
  - AIDS research tool

Genotype: Kit^W-41J related

Reproductive Biology Research
- Fertility Defects
- Gonadal Tumors
  - ovarian
- Developmental Defects Affecting Gonads
  - germ cell deficient
Cancer Research
- Increased Tumor Incidence
  - Gonadal Tumors: ovarian
  - Gonadal Tumors
- Growth Factors/Receptors/Cytokines
- Oncogenes
Mouse/Human Gene Homologs
- piebaldism
Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - Mast Cell Deficiency
Endocrine Deficiency Research
- Skin Defects
- Bone/Bone Marrow Defects
- Gonad Defects
Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
Neurobiology Research
- Receptor Defects
- Hearing Defects
Sensorineural Research
- Hearing Defects
Dermatology Research
- Color and White Spotting Defects
Developmental Biology Research
- Neural Crest Defects

Cancer Research
- Toxicology
  - xenograft/transplant host
  - B and T cell deficiency, xenograft/transplant host
Research Tools
- Cancer Research
  - xenograft/transplant host
- Toxicology Research
  - xenograft/transplant host
- Immunology, Inflammation and Autoimmunity Research
Virology Research
- B and T Cell Deficiency
  - AIDS research tool
Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
Hematological Research
- Immunological Defects
  - B and T cell deficiency

Genotype: Il2rg^tm1Wjl related

Cancer Research
- Growth Factors/Receptors/Cytokines
Immunology, Inflammation and Autoimmunity Research
- Growth Factors/Receptors/Cytokines

Mammalian Phenotype Terms by Genotype

References

Cosgun KN; Rahmig S; Mende N; Reinke S; Hauber I; Schafer C; Petzold A; Weisbach H; Heidkamp G; Purbojo A; Cesnjevar R; Platz A; Bornhauser M; Schmitz M; Dudziak D; Hauber J; Kirberg J; Waskow C. 2014. Kit regulates HSC engraftment across the human-mouse species barrier. Cell Stem Cell 15(2):227-38PubMed: 25017720 MGI: J:232320
Rahmig S; Kronstein-Wiedemann R; Fohgrub J; Kronstein N; Nevmerzhitskaya A; Bornhauser M; Gassmann M; Platz A; Ordemann R; Tonn T; Waskow C. 2016. Improved Human Erythropoiesis and Platelet Formation in Humanized NSGW41 Mice. Stem Cell Reports 7(4):591-601PubMed: 27618723 MGI: J:235122

Additional - Il2rg^tm1Wjl related

Additional - Kit^W-41J related

Additional - Prkdc^scid related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Probe:Il2rg-PROBE
- End Point Analysis:Prkdc End Point
- End Point Analysis:Kit-EP
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice can be bred as homozygotes for the Kit^W-41J, Prkdc^scid, Il2rg^tm1Wjl alleles and the NOD/ShiLtJ Sirpa variant (males would be hemizygous for the X-linked Il2rg^tm1Wjl).
- Additional Breeding and Husbandry Support

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

This Strain is not available for distribution.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:NSGW41

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

KitW-41J

Allele Symbol: KitW-41J

Prkdcscid

Allele Symbol: Prkdcscid

Il2rgtm1Wjl

Allele Symbol: Il2rgtm1Wjl

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Prkdcscid related

Genotype: KitW-41J related

Genotype: Il2rgtm1Wjl related

Mammalian Phenotype Terms by Genotype

References

Additional - Il2rgtm1Wjl related

Additional - KitW-41J related

Additional - Prkdcscid related

Genotyping Protocols

Breeding Considerations

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Kit^W-41J

Allele Symbol: Kit^W-41J

Prkdc^scid

Allele Symbol: Prkdc^scid

Il2rg^tm1Wjl

Allele Symbol: Il2rg^tm1Wjl

Genotype: Prkdc^scid related

Genotype: Kit^W-41J related

Genotype: Il2rg^tm1Wjl related

Additional - Il2rg^tm1Wjl related

Additional - Kit^W-41J related

Additional - Prkdc^scid related