NOD scid gamma (NSG™): The Most Versatile Immunodeficient Mouse

NSG™ mice (005557) are the most highly immunodeficient mice
and the model of choice for cancer xenograft modeling, stem cell
biology, humanized mice, and infectious disease research.

NSG™ Mouse Model Portfolio

Innovative research models, built using the NOD scid gamma (NSG™) mouse

The versatility of NOD scid gamma mice (005557) makes this strain the ideal platform to develop refined genetic models in multiple disease areas including immunology, cancer, transplantation and infectious disease. Innovative mouse strains, built on NSG™, with enhanced transgenic and targeted genetic modifications, allow sophisticated experimentation in multiple research areas.

Immunology

  • NSG™ HLA Class I transgenic strains (009617 and 014570), expressing A2 haplotypes 
    • Permit HLA restriction and enhance immune responses of human CD8 T cells (Strowig, et al. 2009; Shultz, et al. 2010)
  • NSG™ HLA Class II transgenic strains, expressing DR1 (012479) and DR4 (017637) haplotypes
    • Show enhanced antibody responses, and human CD4 T cells interact more effectively with human antigen presenting cells. A NRG DR4 transgenic strain, “DRAG” (017914), is accessible to for-profit entities (Danner R, et al. 2011)
  • NSG™ transgenic human membrane-bound Kit ligand (017830)
    • Improved myeloid engraftment (especially mast cells) and do not require pre-conditioning irradiation before engrafting human hematopoietic stem cells (Brehm, et al. 2012; Takagi, et al. 2012)

  • NSG™ transgenic human IL-3, CSF2, Kit ligand (013062)
  • NOD Rag gamma (NRG) (007799)
    • Radiation-resistant alternative to NSG™ mice
    • Equally effective at engrafting human hematopoietic stem cells and undergoing multilineage hematopoiesis as NSG™ (Pearson, et al. 2008)
  • NSG™ expressing EGFP (021937)
    • Expresses EGFP in all cells of the embryo and adult.
    • Facilitates visualization of allogeneic and xenogeneic grafts

HIV & other infectious diseases

  • NSG™ HLA Class I transgenic strains (009617 and 014570), expressing A2 haplotypes
    • Allow HLA restriction of developing human CD8 cells in humanized models, and provide improved platforms for viral infection and vaccine models (Strowig, et al. 2009; Shultz, et al. 2010)
    • Antibody responses improved in a Dengue virus infection model (Jaiswal, et al. 2012)
  • NSG™ HLA Class II transgenic strains, expressing DR1 (012479) and DR4 (017637) haplotypes
    • Allow HLA restriction of developing human CD4 cells and improve interactions with antigen-presenting cells;
    • Enhanced IgG responses
  • NSG™ mice lacking MHC class I, NSG™ B2m (010636) and NSG™ (KbDb ) null (023848)

Cancer

  • NSG™ transgenic human IL-3, CSF2, Kit ligand (013062)
  • NSG™ Hprt mice (012480)
    • Facilitates isolation of human cancer cells from mouse stroma in vitro, and enable establishment of new patient-derived cell lines (Kamiyama, et al. 2013)
  • NSG™ expressing EGFP (021937)
    • Expresses EGFP in all cells of the embryo and adult
    • Facilitates visualization of allogeneic and xenogeneic grafts

Transplantation research

  • NSG™ lacking MHC class I, NSG™ B2m (010636) and NSG™ (KbDb ) null (023848)
  • NSG™ lacking MHC class II (021885)
  • NSG™ expressing EGFP (021937)
    • Expresses EGFP in all cells of the embryo and adult
    • Facilitates visualization of allogeneic and xenogeneic grafts

Diabetes

  • NRG Akita (014568)
    • Spontaneously develop hyperglycemia and allow engraftment of human pancreatic islets and stem cell therapies for Type 1 Diabetes (Brehm, et al. 2010)

Housing and Breeding Considerations for NSG™ Mice

NSG™ mice are severely immunodeficient and sensitive to infection by a wide range of normal pathogens, opportunistic pathogens, and commensal organisms (Foreman, et al. 2011). Barrier practices that are sufficient to maintain nude and scid colonies may not be adequate for NSG™ mice, however, with the implementation of strict barrier practices and aseptic technique, maintenance of pathogen-free NSG mice is possible and attainable.

Below are some suggestions for ensuring the health status of NSG™ and related immunodeficient strains:

  • All food, water, bedding, and cages entering the room should be autoclaved or sterilized in some way
  • Microisolator or pressurized individually ventilated (PIV) caging is recommended
  • Acidification of water to pH 2.5 – 3.0 helps to prevent infection by Pseudomonas species
  • Personal protective equipment (sterile scrubs, frocks, gloves, masks, and hair coverings) should be worn at all times to cover your skin and minimize chances of spreading bacteria to the mice
  • Handle mice with forceps that have disinfected, and/or with gloved hands that have been sterilized with ethanol
  • Change cages under a laminar flow hood.  Disinfect hands after opening the ventilated cage top, reaching within the cage, or removing your gloved hands from the hood.  Disinfect the hood in between changes
  • Consider changing cages weekly to prevent the introduction of minimal inoculating doses of opportunistic or commensal organisms in the cage environment


NSG™ HEALTH REPORT

Breeding considerations for NOD scid gamma (NSG™) immunodeficient mice


NSG™ mice are good breeders if they are maintained under optimal housing conditions that ensure their health status. Breeding characteristics of our NSG™ colony include:

  • Litter sizes are large (averaging 8 pups per litter) and frequent (most females deliver 7-8 litters over the course of 6 month breeding period) 
  • Breeding performance of NSG™ mice improves when breeding pairs or trios are established at the age of 5-6 weeks 
  • The breeding lifespan of NSG™ mice is not limited by the development of thymic lymphoma as in other scid strains. NSG™ mice can remain productive breeders for as long as one year, and some older breeders can occasionally develop osteosarcomas and mammary carcinomas (Kavirayani and Foreman, 2010). Approximately 90-95% of breeders in our NSG™ colony reach the end of the breeding period at the age of 7-8 months

Frequently Asked NSG™ Questions

Below are common questions and answers for maintaining and using NSG™ mice in biomedical research.  The questions are organized under the following sections:

Basic facts about NSG™ mice

How immunodeficient are NSG™ mice?


NSG™ is one of the most immunodeficient mouse strains described to date.  Here's why:

  • The NOD genetic background contains alleles that reduce the function of the innate branch of the immune system.  Consequently, macrophages and dendritic cells are defective.
  • scid is a loss-of-function mutation of the Prkdc gene that prevents the development of T and B cells.  Prkdc encodes the catalytic subunit of a DNA dependent protein kinase with a role in resolving the DNA double strand breaks that occur during V(D)J recombination.  In the absence of V(D)J recombination, the T cell receptor (TCR) gene in T cells and the immunoglobulin (Ig) gene in B cells are not expressed, and T and B cells cannot mature.
  • The gamma chain of the interleukin 2 receptor (Il2rg) is a common component of the cell surface receptors for six different interleukins (IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21).  NSG™ mice have a complete null mutation (knockout) of this gene.  The signaling pathways for these cytokines are blocked in Il2rg knockout mice, although the cytokines themselves are still present.   The major consequence of Il2rg deficiency is an absence of functional NK cells, which require IL15 signaling to develop.

How long do NSG™ mice live?


NSG™ mice can live over 1.5 years in a sufficiently clean environment (Prof. Lenny Shultz’s first publication about the strain reports a median survival time that exceeds 89 weeks).  They are susceptible to opportunistic pathogens, as discussed below.  They live longer than other scid mice because they do not develop thymic lymphoma (the major cause of death of the parental strain, NOD scid).

Which immune cells remain in NSG™ mice?

Neutrophils and monocytes constitute most of the remaining mouse immune cells detectable in peripheral blood.  Dendritic cells and macrophages are also present in the mouse, although they are defective because of alleles in the NOD/ShiLt genetic background.

What does it mean for NSG™ mice to be “radiation sensitive”?

The gene Prkdc, mutated by scid, enocodes a DNA protein kinase that participates in DNA double strain break repair throughout the body, and not just in developing immune cells.  Consequently, mice that carry the Prkdcscid mutation have increased sensitivity to chemical or physical agents that damage DNA, such as cancer chemotherapies and irradiation. Mice expressing scid require a lower dose of preconditioning irradiation, compared with mice harboring the Rag1 knockout.  On the other hand, they do not tolerate very high doses of radiation.  NSG™ mice tolerate radiation doses up to 400 cGy (4 Gy).  The radiation sensitivity of NSG™ mice might become an issue when studying the response of an engrafted tumor to high-dose radiation treatment.  Furthermore, chemotherapies that act by causing DNA damage can have higher toxicity in scid mice, compared to Rag1 or Rag2 knockouts.  A maximum tolerated dose study is advisable before dosing NSG™ mice with any chemotherapy. 

Are NSG™ mice susceptible to streptozotocin (STZ)?

Yes, NSG™ mice are susceptible to STZ.  STZ is an alkylating agent that kills the insulin producing beta cells in the pancreas, resulting in a state that resembles the end stage of type 1 diabetes.

Where can I go to find more information about NSG™?

  • The JAX strain datasheet has basic information including genotyping protocols. 
  • Breakthrough Research Using NSG™ Mice” lists an annotated, categorized list of publications that is updated weekly.
  • Review the original publication describing the strain.
  • Contact Technical Information Services to discuss further how NSG™ might further your specific research goals

Contact technical support 

Comparisons with other strains

What is a “scid-beige” mouse, and how similar is it to NSG™?

A “scid beige” mouse expresses the same scid mutation found in NSG™, along with the “beige” mutation that impairs NK cells by reduces the degranulation capabilities.  The genetic background is congenic with BALB/c.  The level of immunodeficiency of a scid-beige is probably similar to NOD-scid, but not as high as NSG™.  NSG™ is a better host for humanized immune systems than scid-beige.  scid beige mice are not available from The Jackson Laboratory.

How does NSG™ compare to other strains used in the field?

Most direct comparisons pertain to “humanized mice”.  NSG™ is superior over other models for human CD34+ (stem cell) and PBMC (mature immune cell) engraftment.  Inferior models include:

  • Any strain expressing the scid mutation alone (NOD-scid, B6-scid, C.B17-scid)
  • scid-beige”
  • The same mutations—scid (or a Rag1 or Rag2 knockout) and Il2rg - on other backgrounds (for example, BALB/c)
References: 
    • McDermott SP, et al. 2010. Blood. Jul 15;116(2):193-200. PMID: 20404133
    • Shultz LD et al.  2005.  J Immunol 174(10):6477-89.  PMID: 15879151
    • Lepus CM, et al. 2009. Hum Immunol. Oct;70(10):790-802.  PMID: 19524633

How does scid differ from knockouts of Rag1 or Rag2?

Mice with a knockout of either Rag1 or Rag2 have a very similar phenotype in the immune system (elimination of T and B cells), but they do not have the side effect of radiation/chemotherapy sensitivity.  Rag1 and Rag2 knockout mice have essentially the same phenotype, and a knockout of either gene suffices to eliminate the adaptive immune system.

How does NSG™ compare to NRG?  Why should I use one over the other?

NSG™ and NRG (NOD.Cg-Rag1tm1Mom Il2rgtm1Wjl/SzJ, 007799) are very similar strains.  NRG mice substitute the Rag1 knockout mutation for the scid mutation.  The Rag1 knockout has a very similar phenotype in the immune system (elimination of T and B cells), but it does not have the scid side effect of radiation/chemotherapy sensitivity.

There is one publication comparing NSG™ to NRG in a humanized immune system model created by injection of human CD34+ stem cells.  The recovery of mature human immune cells is essentially the same.

NRG mice do not have the same sensitivity to DNA damage that NSG™ mice do.  NRG could be used in any application that requires especially high doses of radiation.  Note that NSG™ mice do tolerate the radiation doses necessary for human hematopoietic stem cell engraftment. NSG™ mice do not tolerate radiation doses at or above 400cGy (4 Gy), while NRG mice tolerate radiation at doses up to 650 cGy.  Many chemotherapies act by damaging DNA, and the scid mutation also makes a mouse more sensitive to the side effects of chemotherapies.  Although In Vivo Pharmacology Services has successfully dosed NSG™ mice with many different chemotherapies (cisplatin, carboplatin, araC, and others), there may be some instances when NRG mice are preferred if the treatment remains persistently toxic to the mouse.

Husbandry and handling


What pathogens are NSG™ mice susceptible to, and how do they get infected?

NSG™ mice are severely immunodeficient and unable to fight off infections.  They are susceptible to infections by normal mouse pathogens, opportunistic pathogens, and even their own intestinal flora.  They can become infected from injection sites, bite wounds, and any insult that punctures the skin.  The most common type of infection is an ascending urinary tract infection.

How do I keep NSG™ mice healthy?

Proper aseptic handling techniques are essential when working with NSG™ mice.  For more details, please see the “Housing and breeding considerations for NSG™ mice” the FAQ section on this page.

Do NSG™ mice breed well?

Yes, assuming that they are maintained in a sufficiently clean environment.  Poor breeding performance can indicate an infection. For more details, please see the “Housing and breeding considerations for NSG™ mice” the FAQ section on this page.

Do NSG™ mice need antibiotics in their food or water?


We do not maintain NSG™ mice on antibiotics at The Jackson Laboratory.  We find that strict adherence to proper husbandry and handling practices can prevent the introduction of pathogens to the mice, and ensure their long-term survival.

Humanized NSG™ mice


Why are NSG™ mice the best hosts for human hematopoietic stem cells?

What is a “humanized mouse”?


A “humanized mouse” refers either to a mouse that expresses a human gene, or one that contains human cells or tissues.  The most common type of humanized NSG™ mouse is one carrying human immune cells that have either been generated in the mouse (following CD34+ human hematopoietic stem cell injections), or generated in a human donor and injected into the mouse (PBMCs).  

What are CD34+cells and PBMCs?

CD34 is a marker for stem/progenitor cells that are capable of producing every hematopoietic lineage.  When injected in a NSG™ mouse, they naturally migrate to the bone marrow and differentiate into the mature cell types of the immune system, along the established progenitor pathways. 

PBMCs (“peripheral blood mononuclear cells”) include mature lymphocytes (B, T, NK cells), monocytes and macrophages.  When injected in the NSG™ mouse, PBMCs either remain in circulation (T cells), or die/migrate to other tissues (all other cell types).  They are collected from a blood donation, usually from healthy donors, but can be from diseased or sick patients.

Why do NSG™ mice require irradiation before hematopoietic stem cell engraftment?

Treatment with radiation (usually from an X-irradiator or a cesium source) is a prerequisite for efficient colonization of mouse bone marrow by human hematopoietic stem cells.  Irradiation works by killing the mouse stem cells and opening the bone marrow niche, and also by inducing expression of cytokines like Kit ligand (also known as stem cell factor, or SCF).  The preconditioning irradiation dose depends on the age of the mouse and often needs to be optimized in every laboratory. Newborn mice tolerate lower doses than juvenile or adult mice.

Are humanized mice available from The Jackson Laboratory?

Yes, through In Vivo Pharmacology Services.

How long can a CD34-humanized NSG™ mouse remain engrafted with human immune cells?

CD45+ cells (mature white blood cells) have been detected in the peripheral blood as long as one year after injection with CD34+ hematopoietic stem cells. In the experience of JAX In Vivo Pharmacology Services, there are no signs of graft-versus-host disease when T-cell-depleted stem cells are sourced from cord blood in mice for up to one year post-engraftment.

How functional is the human immune system that develops in a CD34-injected NSG™?

The different cell types that make up the lymphoid and myeloid lineages are present within humanized NSG™ mice, and there is a significant amount of effort going into understanding how functional they are.  Here’s a summary of some key findings:

Other analyses of the different lineages can be found in the online categorized list of references.

What is graft-versus-host disease?  When does it occur?


Graft-versus-host-disease (GVHD) occurs when mature immune cells mount an immune attack on the mouse.  This is a possibility any time the immune cells are sourced directly from human blood (PBMCs).  It also happens when mature mouse immune cells are injected, if the cells come from any strain with a background other than NOD/ShiLt.  GVHD usually sets in within 3-4 weeks after injection of human PBMCs.  NSG™ mice without MHC class I show delayed onset of GVHD.

When can a humanized NSG™ mouse be used for vaccine studies?

To function in a vaccine model, the human T cells in the mouse must be able to interact efficiently with human antigen presenting cells, such as dendritic cells.   This phenomenon is known as “HLA restriction” (HLA is the human counterpart to the mouse MHC).  Unless the human T cells have developed in a transgenic mouse expressing human HLA, or in a mouse with a human thymus implant, then the interactions are not efficient, and the humanized immune system is probably not capable of mounting an efficient immune response to a vaccination.

What are HLA (human MHC) transgenic NSG™ mice?  What are their research applications?

Expression of human MHC (“HLA”) class I improves the function of cytotoxic T cells (CD8+ cells).  This is useful for studies involving infectious diseases that infect human immune cells (Epstein-Barr virus, for example), because this response is largely control by cytotoxic T cells.  NOD.Cg-Prkdcscid Il2rgtm1Wjl Tg(HLA-A2.1)1Enge/SzJ (Stock # 009617) and NOD.Cg-Prkdcscid Il2rgtm1Wjl Tg(HLA-A/H2-D/B2M)1Dvs/SzJ (Stock # 014570) are two strains that express the HLA-A2.1 class I haplotype.

Expression of human MHC (“HLA”) class II improves the function of helper T cells (CD4+ cells).  This should be useful for vaccine studies.  NOD.Cg-Prkdcscid Il2rgtm1Wjl Tg(HLA-DRA*0101,HLA-DRB1*0101)1Dmz/GckRolyJ (Stock # 012479) and NOD.Cg-Prkdcscid Il2rgtm1Wjl H2-Ab1tm1Gru Tg(HLA-DRB1)31Dmz/SzJ (Stock # 017637) are two examples.  The second strain does not express the endogenous mouse MHC class2 complex.

Do NSG™ mice require irradiation before injecting PBMCs?

No.  Only hematopoietic stem cells require preconditioning irradiation for efficient engraftment.  Irradiation accelerates the GVHD response.

Where can I find protocols describing humanized NSG™ mice?

Below is a list of publications that describe protocols and considerations for creating humanized NSG™ mice.  Pearson, et al. 2008 is especially recommended.

  • McDermott SP, et al. 2010. Comparison of human cord blood engraftment between immunocompromised mouse strains. Blood. Jul 15;116(2):193-200  [PubMed ID: 20404133]
  • Brehm MA, et al.. 2010. Parameters for establishing humanized mouse models to study human immunity: analysis of human hematopoietic stem cell engraftment in three immunodeficient strains of mice bearing the IL2rgamma(null) mutation. Clin Immunol. Apr;135(1):84-98. [PubMed ID: 20096637]
  • Pearson T, et al. 2008. Creation of "humanized" mice to study human immunity. Curr Protoc Immunol. May; Chapter 15:Unit 15.21. [PubMed: 18491294]

Applications in Cancer Research


Which cancer xenograft models benefit from using NSG™ mice?


Certain cancer models are established more efficiently in NSG™ mice compared to other strains:
  • Hematopoietic cancers (leukemia in particular) engraft significantly better in NSG™ compared to other strains.  That includes leukemia cell lines and patient-derived samples
  • Most solid cancer cell lines probably do not require the severe immunodeficiency of NSG™; however, you may find that cell lines that do not grow well in other strains grow better in NSG™.  
  • ER+ breast cancer xenografts, for reasons discussed below.   

Can NSG™ mice support the growth of patient-derived or clinical tumor samples?


Yes.  JAX In Vivo Pharmacology Services has had great success establishing diverse types of patient-derived tumor models in NSG™ mice, including leukemia models.  Slow-growing tumors benefit from the long lifespan of NSG™ mice.  Lung and ovarian PDX models are described in the literature, as is a publication that utilizes bladder cancer PDX samples from our tumor bank. 

Are NSG™ mice suitable for cancer stem cell studies?


Yes.  NSG™ has emerged as the preferred platform for studying the frequency and characteristics of cancer stem cells.  This is a consequence of its greater degree of immunodeficiency, and in many instances this results in a more permissive environment for cancer stem cells to grow.  Here are examples from melanoma, leukemia, and many other tumor types.  NSG™ mice have enabled some important discoveries, especially for melanoma and acute myeloid leukemia.

Why are NSG™ mice good xenografts hosts for ER+ breast cancer?


Estrogen receptor (ER) positive breast cancers require estrogen (estradiol) supplementation to retain ER positivity in a xenograft setting.  NSG™ mice are more resistant to the toxic side effects of estradiol supplementation compared to other strains, including nude and NOD-scid.  This enables long-term study of ER+ breast cancer xenografts.

Breakthrough Research Using NSG™

Below is an expanding list of publications that highlight advances using NSG™ mice in key research areas, including:  

  • Immunology
  • Infectious disease
  • Solid tumors
  • Hematological cancers
  • Diabetes
  • Stem cells / regenerative medicine
  • Miscellaneous

Immunology


Humanized immune system: hematopoiesis and stem cell engraftment
Amabile G; Welner RS; Nombela-Arrieta C; D'Alise AM; Di Ruscio A; Ebralidze AK; Kraytsberg Y; Ye M; Kocher O; Neuberg DS; Khrapko K; Silberstein LE; Tenen DG. 2013. In vivo generation of transplantable human hematopoietic cells from induced pluripotent stem cells. Blood. Feb 21;121(8):1255-64. [PubMed: 23212524]

André MC; Erbacher A; Gille C; Schmauke V; Goecke B; Hohberger A; Mang P; Wilhelm A; Mueller I; Herr W; Lang P; Handgretinger R; Hartwig UF. 2010. Long-Term Human CD34+ Stem Cell-Engrafted Nonobese Diabetic/SCID/IL-2 gamma-null Mice Show Impaired CD8+ T Cell Maintenance and a Functional Arrest of Immature NK Cells. J Immunol Sep 1;185(5):2710-20. [PubMed: 20668220]

Baerenwaldt A; Lux A; Danzer H; Spriewald BM; Ullrich E; Heidkamp G; Dudziak D; Nimmerjahn F. 2011. Fcγ receptor IIB (FcγRIIB) maintains humoral tolerance in the human immune system in vivo. Proc Natl Acad Sci U S A Nov 15;108(46):18772-7. [PubMed: 22065769

Bartee E; Meacham A; Wise E; Cogle CR; McFadden G. 2012 Virotherapy Using Myxoma Virus Prevents Lethal Graft-versus-Host Disease following Xeno-Transplantation with Primary Human Hematopoietic Stem Cells. PLoS One.7(8):e43298. [PubMed: 22905251]

Baudet A; Karlsson C; Safaee Talkhoncheh M; Galeev R; Magnusson M; Larsson J. 2012. RNAi screen identifies MAPK14 as a druggable suppressor of human hematopoietic stem cell expansion. Blood. Jun 28;119(26):6255-8. [PubMed: 22555972]

Belle L; Bruck F; Foguenne J; Gothot A; Beguin Y; Baron F; Briquet A. 2012. Imatinib and Nilotinib Inhibit Hematopoietic Progenitor Cell Growth, but Do Not Prevent Adhesion, Migration and Engraftment of Human Cord Blood CD34(+) Cells. PLoS One. 7(12):e52564. [PubMed: 23285088]

Bernink JH; Peters CP; Munneke M; Te Velde AA; Meijer SL; Weijer K; Hreggvidsdottir HS; Heinsbroek SE; Legrand N; Buskens CJ; Bemelman WA; Mjösberg JM; Spits H. 2013. Human type 1 innate lymphoid cells accumulate in inflamed mucosal tissues. Nat Immunol  Mar;14(3):221-9. [PubMed: 23334791]
Demonstrates induction of inflammatory bowel disease with DSS in humanized NSG

Boitano AE; Wang J; Romeo R; Bouchez LC; Parker AE; Sutton SE; Walker JR; Flaveny CA; Perdew GH; Denison MS; Schultz PG; Cooke MP. 2010. Aryl Hydrocarbon Receptor Antagonists Promote the Expansion of Human Hematopoietic Stem Cells. Science Sep 10;329(5997):1345-58. [PubMed: 20688981]

Broxmeyer HE; Lee MR; Hangoc G; Cooper S; Prasain N; Kim YJ; Mallett C; Ye Z; Witting S; Cornetta K; Cheng L; Yoder MC. 2011. Hematopoietic stem/progenitor cells; generation of induced pluripotent stem cells; and isolation of endothelial progenitors from 21-23.5 year cryopreserved cord blood. Blood May 5;117(18):4773-7. [PubMed: 21393480]

Bueno C; Montes R; de la Cueva T; Gutierrez-Aránda I; Menendez P. 2010. Intra-bone marrow transplantation of human CD34(+) cells into NOD/LtSz-scid IL-2rgamma(null) mice permits multilineage engraftment without previous irradiation. Cytotherapy 12(1):45-9. [PubMed: 19929453]

Butler JM; Gars EJ; James DJ; Nolan DJ; Scandura JM; Rafii S. 2012. Development of a vascular platform for expansion of repopulating human cord blood stem and progenitor cells. Blood. Aug 9;120(6):1344-7 [PubMed: 22709690]

Cai S; Wang H; Bailey B; Ernstberger A; Juliar BE; Sinn AL; Chan RJ; Jones DR; Mayo LD; Baluyut AR; Goebel WS; Pollok KE. 2011. Humanized Bone Marrow Mouse Model as a Preclinical Tool to Assess Therapy-Mediated Hematotoxicity. Clin Cancer Res Apr 15;17(8):2195-2206. [PubMed: 21487065]
This publication shows how humanized NSG mice can be used to screen for bone marrow toxicity and myelosuppresion

Capitano ML; Hangoc G; Cooper S; Broxmeyer HE. Mild heat treatment primes human CD34+ cord blood cells for migration towards SDF-1α and enhances engraftment in an NSG mouse model. Stem Cells. 2015 Mar 5. Epub ahead of print. [PubMed: 25753525]

Ceccaldi R; Parmar K; Mouly E; Delord M; Kim JM; Regairaz M; Pla M; Vasquez N; Zhang QS; Pondarre C; Peffault de Latour R; Gluckman E; Cavazzana-Calvo M; Leblanc T; Larghero J; Grompe M; Socié G; D'Andrea AD; Soulier J. 2012. Bone Marrow Failure in Fanconi Anemia Is Triggered by an Exacerbated p53/p21 DNA Damage Response that Impairs Hematopoietic Stem and Progenitor Cells. Stem Cells. Jul 6;11(1):36-49. [PubMed: 22683204]

Chen Q; Khoury M; Limmon G; Choolani M; Chan JK; Chen J. 2013. Human Fetal Hepatic Progenitor Cells Are Distinct from, but Closely Related to, Hematopoietic Stem/Progenitor Cells. Stem Cells. Jun;31(6):1160-9. [PubMed: 23404852]

Chen Q; He F; Kwang J; Chan JK; Chen J. 2012. GM-CSF and IL-4 Stimulate Antibody Responses in Humanized Mice by Promoting T, B, and Dendritic Cell Maturation. J Immunol. Dec 1;189(11):5223-9. [PubMed: 23089398]
Hydrodynamic tail vain delivery of human cytokines improves immune cell function

Csaszar E; Kirouac DC; Yu M; Wang W; Qiao W; Cooke MP; Boitano AE; Ito C; Zandstra PW. 2012. Rapid expansion of human hematopoietic stem cells by automated control of inhibitory feedback signaling. Stem Cells Feb 3;10(2):218-29. [PubMed: 22305571]

Drake AC; Khoury M; Leskov I; Iliopoulou BP; Fragoso M; Lodish H; Chen J. 2011. Human CD34+ CD133+ Hematopoietic Stem Cells Cultured with Growth Factors Including Angptl5 Efficiently Engraft Adult NOD-SCID Il2rγ-/- (NSG) Mice. PLoS One Apr 29;6(4):e18382. [PubMed: 21559522]

Doulatov S; Notta F; Eppert K; Nguyen LT; Ohashi PS; Dick JE. 2010. Revised map of the human progenitor hierarchy shows the origin of macrophages and dendritic cells in early lymphoid development. Nat Immunol Jul;11(7):585-93. [PubMed: 20543838]
An elegant example of how the humanized NSG™ model can answer fundamental questions about the origin of hematopoietic progenitors

Eldjerou LK; Chaudhury S; Baisre-de Leon A; He M; Arcila ME; Heller G; O'Reilly RJ; Barker JN; Moore MA. 2010. An in vivo model of double unit cord blood transplantation that correlates with clinical engraftment. Blood Nov 11;116(19):3999-4006. [PubMed: 20587781]

Gao H; Wu X; Sun Y; Zhou S; Silberstein LE; Zhu Z. 2012. Suppression of Homeobox Transcription Factor VentX Promotes Expansion of Human Hematopoietic Stem/Multipotent Progenitor Cells. J Biol Chem Aug 24;287(35):29979-87. [PubMed: 22791709]

Giassi LJ; Pearson T; Shultz LD; Laning J; Biber K; Kraus M; Woda BA; Schmidt MR; Woodland RT; Rossini AA; Greiner DL. 2008. Expanded CD34+ human umbilical cord blood cells generate multiple lymphohematopoietic lineages in NOD-scid IL2rgamma(null) mice. Exp Biol Med (Maywood) 233(8):997-1012. [PubMed: 18653783]

Görgens A; Beckmann J; Ludwig AK; Möllmann M; Dürig J; Horn PA; Rajendran L; Giebel B. 2012. Lipid raft redistribution and morphological cell polarization are separable processes providing a basis for hematopoietic stem and progenitor cell migration. Int J Biochem Cell Biol Jul;44(7):1121-32. [PubMed: 22504287]

Halim TY; Maclaren A; Romanish MT; Gold MJ; McNagny KM; Takei F. 2012. Retinoic-Acid-Receptor-Related Orphan Nuclear Receptor Alpha Is Required for Natural Helper Cell Development and Allergic Inflammation. Immunity. Sep 21;37(3):463-74. [PubMed: 22981535]

Hayakawa J; Hsieh MM; Uchida N; Phang O; Tisdale JF. 2009. Busulfan produces efficient human cell engraftment in NOD/LtSz-Scid IL2Rgamma(null) mice. Stem Cells 27(1):175-82. [PubMed: 18927475]
This publication shows that busulfan is an alternative to pre-conditioning irradiation in the humanized immunity model

Himburg HA; Harris JR; Ito T; Daher P; Russell JL; Quarmyne M; Doan PL; Helms K; Nakamura M; Fixsen E; Herradon G; Reya T; Chao NJ; Harroch S; Chute JP. 2012. Pleiotrophin Regulates the Retention and Self-Renewal of Hematopoietic Stem Cells in the Bone Marrow Vascular Niche. Cell Rep Oct 25;2(4):964-75.[PubMed: 23084748]

Huang J; Nguyen-McCarty M; Hexner EO; Danet-Desnoyers G; Klein PS. 2012. Maintenance of hematopoietic stem cells through regulation of Wnt and mTOR pathways. Nat Med. Dec 6;18(12):1778-85. [PubMed: 23142822]

Isern J; Martín-Antonio B; Ghazanfari R; Martín AM; López JA; Del Toro R; Sánchez-Aguilera A; Arranz L; Martín-Pérez D; Suárez-Lledó M; Marín P; Van Pel M; Fibbe WE; Vázquez J; Scheding S; Urbano-Ispizúa A; Méndez-Ferrer S. 2013. Self-Renewing Human Bone Marrow Mesenspheres Promote Hematopoietic Stem Cell Expansion. Cell Rep. May 30;3(5):1714-24. [PubMed: 23623496]

Ishikawa F; Shimazu H; Shultz LD; Fukata M; Nakamura R; Lyons B; Shimoda K; Shimoda S; Kanemaru T; Nakamura K; Ito H; Kaji Y; Perry AC; Harada M. 2006. Purified human hematopoietic stem cells contribute to the generation of cardiomyocytes through cell fusion. FASEB J 20(7):950-2. [PubMed: 16585061]

Ishikawa F; Yasukawa M; Lyons B; Yoshida S; Miyamoto T; Yoshimoto G; Watanabe T; Akashi K; Shultz LD; Harada M. 2005. Development of functional human blood and immune systems in NOD/SCID/IL2 receptor {gamma} chain(null) mice. Blood 106(5):1565-73. [PubMed: 15920010]
This early NSG™ publication has a thorough characterization of the immune system functions in CD34-humanized mice

Ivanovs A; Rybtsov S; Welch L; Anderson RA; Turner ML; Medvinsky A. 2011. Highly potent human hematopoietic stem cells first emerge in the intraembryonic aorta-gonad-mesonephros region. J Exp Med Nov 21;208(12):2417-27. [PubMed: 22042975]
Shows that a single human hematopoietic stem can engraft, expand, and differentiate in NSG; also shows that the HSC can be re-transplanted

Kalscheuer H; Danzl N; Onoe T; Faust T; Winchester R; Goland R; Greenberg E; Spitzer TR; Savage DG; Tahara H; Choi G; Yang YG; Sykes M. 2012. A model for personalized in vivo analysis of human immune responsiveness. Sci Transl Med. Mar 14;4(125):125ra30. [PubMed: 22422991]
Describes techniques for engrafting bone marrow aspirate HSCs from healthy and type 1 diabetic individuals; also demonstrates improved adult HSC engraftment with thymus implants

Kim I; Kim YJ; Métais JY; Dunbar CE; Larochelle A. 2012. Transient silencing of PTEN in human CD34(+) cells enhances their proliferative potential and ability to engraft immunodeficient mice. Exp Hematol Jan;40(1):84-91 [PubMed:22019626]

Kohn LA; Hao QL; Sasidharan R; Parekh C; Ge S; Zhu Y; Mikkola HK; Crooks GM 2012. Lymphoid priming in human bone marrow begins before expression of CD10 with upregulation of L-selectin. Nat Immunol. Oct;13(10):963-71.[PubMed:22941246]

Larochelle A; Savona M; Wiggins M; Anderson S; Ichwan B; Keyvanfar K; Morrison SJ; Dunbar CE. 2011. Human and rhesus macaque hematopoietic stem cells cannot be purified based only upon SLAM family markers. Blood Feb 3;117(5):1550-4. [PubMed: 21163926]

Larochelle A; Gillette JM; Desmond R; Ichwan B; Cantilena A; Cerf A; Barrett AJ; Wayne AS; Lippincott-Schwartz J; Dunbar CE. 2012. Bone marrow homing and engraftment of human hematopoietic stem and progenitor cells is mediated by a polarized membrane domain. Blood Feb 23;119(8):1848-55. [PubMed: 22228628]

Laurenti E; Doulatov S; Zandi S; Plumb I; Chen J; April C; Fan JB; Dick JE. 2013. The transcriptional architecture of early human hematopoiesis identifies multilevel control of lymphoid commitment. Nat Immunol. Jul;14(7):756-63. [PubMed ID:23708252]

Lecourt S; Mouly E; Freida D; Cras A; Ceccaldi R; Heraoui D; Chomienne C; Marolleau JP; Arnulf B; Porcher R; Caillaud C; Vanneaux V; Belmatoug N; Larghero J. 2013. A prospective study of bone marrow hematopoietic and mesenchymal stem cells in type 1 Gaucher disease patients. PLoS One. Jul 25;8(7):e69293. [PubMed ID: 23935976]

Lee J; Li M; Milwid J; Dunham J; Vinegoni C; Gorbatov R; Iwamoto Y; Wang F; Shen K; Hatfield K; Enger M; Shafiee S; McCormack E; Ebert BL; Weissleder R; Yarmush ML; Parekkadan B. 2012. Implantable microenvironments to attract hematopoietic stem/cancer cells. Proc Natl Acad Sci U S A. Nov 27;109(48):19638-43. [PubMed: 23150542]

Li L; Modi H; McDonald T; Rossi J; Yee JK; Bhatia R. 2011. A critical role for SHP2 in STAT5 activation and growth factor mediated proliferation; survival and differentiation of human CD34+ cells. Blood Aug 11;118(6):1504-15. [PubMed:21670473]

Liu C; Chen BJ; Deoliveira D; Sempowski GD; Chao NJ; Storms RW. 2010. Progenitor cell dose determines the pace and completeness of engraftment in a xenograft model for cord blood transplantation. Blood Dec 16;116(25):5518-27. [PubMed: 20833978]

Lockridge JL; Zhou Y; Becker YA; Ma S; Kenney SC; Hematti P; Capitini CM; Burlingham WJ; Gendron-Fitzpatrick A; Gumperz JE. 2013. Mice Engrafted with Human Fetal Thymic Tissue and Hematopoietic Stem Cells Develop Pathology Resembling Chronic Graft-versus-Host Disease. Biol Blood Marrow Transplant. Sep;19(9):1310-22. [PubMed ID:23806772]

Magnusson M; Sierra MI; Sasidharan R; Prashad SL; Romero M; Saarikoski P; Van Handel B; Huang A; Li X; Mikkola HK. 2013. Expansion on stromal cells preserves the undifferentiated state of human hematopoietic stem cells despite compromised reconstitution ability. PLoS One. 2013;8(1):e53912. [PubMed: 23342037]

Majeti R; Park CY; Weissman IL. 2007. Identification of a hierarchy of multipotent hematopoietic progenitors in human cord blood. Cell Stem Cell 1(6):635-45. [PubMed: 18371405]
This is one of the earliest publications to use NSG mice to study the hematopoietic potential of human stem and progenitor cells

Masuda H; Anwar SS; Bühring HJ; Rao JR; Gargett CE. 2012. A novel marker of human endometrial mesenchymal stem-like cells. Cell Transplant 21(10):2201-14. [PubMed: 22469435]

McIntosh BE; Brown ME; Duffin BM; Maufort JP; Vereide DT; Slukvin II; Thomson JA. 2015. Nonirradiated NOD;B6.SCID Il2rγ-/-KitW41/W41 (NBSGW) Mice Support Multilineage Engraftment of Human Hematopoietic Cells. Stem Cell Reports. Epub ahead of print. [PubMed: 25601207]

Misharin AV; Haines GK 3rd; Rose S; Gierut AK; Hotchkiss RS; Perlman H. 2012. Development of a new humanized mouse model to study acute inflammatory arthritis. J Transl Med. Sep 13;10:190. [PubMed: 22974474]
Validates a humanized model of arthritis, dependent on human T cells and sensitive to TNF alpha inhibition

Notta F; Doulatov S; Dick JE. 2010. Engraftment of human hematopoietic stem cells is more efficient in female NOD/SCID/IL-2Rgcnull recipients. Blood May 115(18): 3704-7 [PubMed: 20207983]
Females are preferentially used for humanized immunity models.

Pang WW; Price EA; Sahoo D; Beerman I; Maloney WJ; Rossi DJ; Schrier SL; Weissman IL. 2011. Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age. Proc Natl Acad Sci U S A. Dec 13;108(50):20012-7. [PubMed: 22123971]

Parcelier A; Maharzi N; Delord M; Robledo-Sarmiento M; Nelson E; Belakhdar-Mekid H; Pla M; Kuranda K; Parietti V; Goodhardt M; Legrand N; Bernstein ID; Gluckman JC; Sigaux F; Canque B. 2011. AF1q/MLLT11 regulates the emergence of human prothymocytes through cooperative interaction with the Notch signaling pathway. Blood Aug 18;118(7):1784-96 [PubMed: 21715312]

Patton J; Vuyyuru R; Siglin A; Root M; Manser T. Evaluation of the efficiency of human immune system reconstitution in NSG mice and NSG mice containing a human HLA.A2 transgene using hematopoietic stem cells purified from different sources. J Immunol Methods. 2015 Mar 14. Epub ahead of print. [PubMed: 25776756]

Robinson SN; Simmons PJ; Thomas MW; Brouard N; Javni JA; Trilok S; Shim JS; Yang H; Steiner D; Decker WK; Xing D; Shultz LD; Savoldo B; Dotti G; Bollard CM; Miller L; Champlin RE; Shpall EJ; Zweidler-McKay PA. 2013. Ex vivo fucosylation improves human cord blood engraftment in NOD-SCID IL-2Rγ(null) mice. Exp Hematol. Jun;40(6):445-56. [PubMed: 22306295]

Risueño RM; Sachlos E; Lee JH; Lee JB; Hong SH; Szabo E; Bhatia M. 2012. Inability of human induced pluripotent stem cell-hematopoietic derivatives to downregulate microRNAs in vivo reveals a block in xenograft hematopoietic regeneration. Stem Cells Feb;30(2):131-9. [PubMed: 22131151]
This publication highlights NSG as a sensitive platform for studying the hematopoietic potential of iPS-derived stem cells.

Rohrabaugh SL; Campbell TB; Hangoc G; Broxmeyer HE. 2011. Ex vivo rapamycin treatment of human cord blood CD34(+) cells enhances their engraftment of NSG mice. Blood Cells Mol Dis Apr 15;46(4):318-20. [PubMed: 21411351]

Rörby E; Nifelt Hägerström M; Blank U; Karlsson G; Karlsson S. 2012. Human hematopoietic stem/progenitor cells overexpressing Smad4 exhibit impaired reconstitution potential in vivo. Blood. Nov 22;120(22):4343-51. [PubMed:23018642]

Scholbach J; Schulz A; Westphal F; Egger D; Wege AK; Patties I; Köberle M; Sack U; Lange F. 2012. Comparison of hematopoietic stem cells derived from fresh and cryopreserved whole cord blood in the generation of humanized mice. PLoS One. 7(10):e46772. [PubMed: 23071634]

Seré K; Baek JH; Ober-Blöbaum J; Müller-Newen G; Tacke F; Yokota Y; Zenke M; Hieronymus T. 2012. Two Distinct Types of Langerhans Cells Populate the Skin during Steady State and Inflammation. Immunity. Nov 16;37(5):905-16. [PubMed: 23159228]

Song L; Li X; Jayandharan GR; Wang Y; Aslanidi GV; Ling C; Zhong L; Gao G; Yoder MC; Ling C; Tan M; Srivastava A. 2013. High-Efficiency Transduction of Primary Human Hematopoietic Stem Cells and Erythroid Lineage-Restricted Expression by Optimized AAV6 Serotype Vectors In Vitro and in a Murine Xenograft Model In Vivo. PLoS One. 8(3):e58757. [PubMed: 23516552]

Tormin A; Li O; Brune JC; Walsh S; Schütz B; Ehinger M; Ditzel N; Kassem M; Scheding S. 2011. CD146 expression on primary non-hematopoietic bone marrow stem cells correlates to in situ localization. Blood May 12;117(19):5067-77. [PubMed: 21415267]

van der Garde M; van Hensbergen Y; Brand A; Slot MC; de Graaf-Dijkstra A; Mulder A; Watt SM; Zwaginga JJ. 2014. Thrombopoietin Treatment of One Graft in a Double Cord Blood Transplant Provides Early Platelet Recovery While Contributing to Long-Term Engraftment in NSG Mice. Stem Cells Dev. Sep; Epub ahead of print. [PMID: 25137252]

Vatakis DN; Bristol GC; Kim SG; Levin B; Liu W; Radu CG; Kitchen SG; Zack JA. 2012. Using the BLT Humanized Mouse as a Stem Cell based Gene Therapy Tumor Model. J Vis Exp. Dec 18;(70). pii: 4181. [PubMed: 23271478]

Wong WM; Sigvardsson M; Astrand-Grundström I; Hogge D; Larsson J; Qian H; Ekblom M. 2012. Expression of Integrin A2 Receptor in Human Cord Blood Cd34+Cd38-Cd90+ Stem Cells Engrafting Long-Term in Nod/Scid-Il2rγ(C) Null Mice. Stem Cells. Feb;31(2):360-71. [PubMed: 23165626]

Zhang J; Barefoot BE; Mo W; Deoliveira D; Son J; Cui X; Ramsburg E; Chen BJ. 2012. CD62L- memory T cells enhance T-cell regeneration after allogeneic stem cell transplantation by eliminating host resistance in mice. Blood. Jun 28;119(26):6344-53. [PubMed: 22596261]

Zibara K; Hamdan R; Dib L; Sindet-Pedersen S; Kharfan-Dabaja M; Bazarbachi A; El-Sabban M. 2012. Acellular bone marrow extracts significantly enhance engraftment levels of human hematopoietic stem cells in mouse xeno-transplantation models. PLoS One 7(7):e40140. [PubMed: 22768336]

Zou J; Sweeney CL; Chou BK; Choi U; Pan J; Wang H; Dowey SN; Cheng L; Malech HL. Oxidase deficient neutrophils from X-linked chronic granulomatous disease iPS cells: functional correction by zinc finger nuclease mediated safe harbor targeting. Blood May 26;117(21):5561-72 [PubMed: 21411759]




Immunodeficient Mouse and Xenograft Host Comparisons

From the most highly immunodeficient mouse available— NSG™ (005557) - to nude mice (002019), the JAX immunodeficient suite of mice are powerful xenograft models for studying solid and hematopoietic tumors, cancer stem cells, hematopoeisis, humanized mice and infectious disease.

Comparison table:

Name & Stock Number NOD.Cg-Prkdcscid
Il2rgtm1Wjl
/SzJ
(005557)
NOD.Cg-Rag1tm1Mom
Il2rgtm1Wjl
/SzJ
(007799
NOD.Cg-Prkdcscid
Il2rgtm1Wjl
Tg(CMV-IL3,CSF2,KITLG)1Eav/MloySzJ
(013062
 NOD.CB17-Prkdcscid/J (001303)
Common name NSG™, NOD scid gamma NRG, NOD Rag gamma NSGS, NOD scid gamma Il3- GM-SF (NSG-SGM3) NOD scid
Mature B cells Absent Absent Absent Absent
Mature T cells Absent Absent Absent Absent
Dendritic cells Defective Defective Defective Defective
Macrophages Defective Defective Defective Defective
Natural killer cells  Absent Absent Absent Defective
Complement Absent Absent Absent Absent
Leakiness Very Low Absent Absent Low
Irradiation tolerance Low High Low Low
Lymphoma incidence Low Low Low High (thymic lymphoma)
Median survival > 89 weeks Not determined Not determined 36 weeks
Benefits
  • Adoptive transfer recipient for study of autoimmune type 1 diabetes 
  • Supports engraftment of human peripheral blood & bone marrow 
  • Xenotransplantation of human tissues, cells & tumors
  • Long-term multilineage hematopoeitic stem cell repopulation similar to NSG mice
  • Engrafts human PBMC without irradiation similar to NSG
  • Engrafts a wide range if solid and hematological cancers

  • Increased CD4+ FoxP3+ regulatory T cell population
  • Enhances human myelopoiesis and terminal differentiation
  • Increased efficiency of engrafting human acute myeloid leukemia (AML)
  • Adoptive transfer recipient for study of autoimmune type 1 diabetes 
  • Engrafts hematopoietic cancer cell lines 
  • Xenotransplantation of some human tumors 

Considerations
  • No thymic lymphomas, can be used for long & short-term experiments 
  • Sensitive to irradiation 
  • No thymic lymphomas, can be used for long & short-term experiments 
  • Requires higher dose of irradiation to obtain human HSC engraftment

  • Compromised human stem cell regeneration
  • Suppression of human erythropoiesis
  • Reduction of human B-lymphopoiesis
  • Develops thymic lymphomas by 8-9 months, best used in short term experiments 
  • Sensitive to irradiation 

References

Ishikawa et al. 2005;
Shultz et al. 2005

Pearson et al. 2008;
Brehm et al. 2010;
Maykel et al. 2014

Nicolini et al. 2004;
Wunderlich et al. 2010;
Billerbeck et al. 2015

Shultz et al. 1995

Comparison table (con't):

Name & Stock Number CBySmn.CB17-Prkdcscid/J (001803)
 
 B6.129S7-Rag1tm1Mom/J (002216)  J:NU (007850) NU/J (002019)
Common name BALB scid B6 Rag1 Nude Nude
Mature B cells Absent Absent Present Present
Mature T cells Absent Absent Absent Absent
Dendritic cells Present Present Present Present
Macrophages Present Present Present Present
Natural killer cells  Present Present Present Present
Complement Present Present Present Present
Leakiness Low Absent N/A N/A
Irradiation tolerance Low High High High
Lymphoma incidence High (thymic lymphoma) Low Low Low
Median survival Not determined Not determined Not determined Not determined
Benefits
  •  MHC haplotype (H2d) allows adoptive transfer from BALB/c donors 
  • Common BALB/cBy inbred background simplifies creation of compound immunodeficient mutants 
  • Therapeutic Ab testing 
  • Engrafts hematopoietic cancer cell lines, some primary cells 

  • MHC haplotype (H2b) allows adoptive transfer from B6 donors 
  • Common B6 inbred background simplifies creation of compound immunodeficient mutants 
  • Theapeutic Ab testing 

  • Engraftment of human & mouse tumor cell lines 
  • Well published/characterized 
  • Uniform genetics improve reproducibility 
  • Hairless phenotype enhances assessment of tumor growth 


  • Engraftment of human & mouse tumor cell lines 
  • Well published/characterized 
  • Uniform genetics improve reproducibility 
  • Hairless phenotype enhances assessment of tumor growth 


Considerations
  • Innate immunity intact 
  • NK cell activity limits engraftment 
  • Sensitive to irradiation 

  • Innate immunity intact 
  • Poor host for primary cell transplantation 

  • Innate immunity intact 
  • Little engraftment of hematopoietic cancer cells 
  • Not suitable for primary cell transplantation 

  • Innate immunity intact 
  • Little engraftment of hematopoietic cancer cells 
  • Not suitable for primary cell transplantation 

References Nonoyama et al. 1993 Mombaerts et al. 1992 Kelland LR. 2004 Kelland LR. 2004

NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (005557) 

The most powerful immunodeficient model that has changed the face of oncology, stem cell and infectious disease research.

  • Commonly known as “NSG™” or “NOD scid gamma” (Shultz et al. 2005
  • Severe defects in innate and adaptive immunity 
  • Lacks mature T, B, and functional NK cells 
  • Deficient in signaling of multiple cytokines (IL2, IL4, IL7, IL9, IL15 and IL21), resulting in significantly improved engraftment of human tissues, hematopoietic stem cells, and peripheral blood mononuclear cells 
  • Resistant to lymphoma, allowing for long-term experiments 
  • Capable of maintaining a human tumor microenvironment after engraftment 
  • Low tolerance for irradiation

NOD.Cg-Rag1tm1MomIl2rgtm1Wjl/SzJ (007799)

  • Commonly known as “NSG™” or “NOD scid gamma” (Pearson et al. 2008
  • Severe defects in innate and adaptive immunity 
  • Lacks mature T, B, and functional NK cells
  • Engrafts human PBMC without irradiation
  • Tolerant to irradiation

NOD.Cg-PrkdscidIl2rgtm1WjlTg(CMV-IL3,CSF2,KITLG)1Eav/MloySzJ/ (013062)

  • Commonly known as "NSGS" or "NSG-SGM3"
  • The expression of several transgenic human cytokines supports higher levels of human myeloid cell expansion
  • Significant engraftment of patient-derived AML samples

NOD.CB17-Prkdcscid/J (001303)

  • Commonly called “NOD scid” (Shultz  et al. 1995
  • Lack functional T and B cells 
  • Thymus, lymph node, and spleen virtually devoid of lymphocytes 
  • NOD genetic background results in reduced NK cell activity, impaired complement pathway, and least “leakiness” of residual T and B cells of any scid strain
  • Accepts allogeneic and xenogeneic grafts very efficiently and has been used successfully to transplant a variety of normal and malignant human cells and tissues, including isolates from hematopoietic cancers 
  • Insulitis - and diabetes-free throughout life 
  • Often develops thymic lymphomas by eight and a half months 
  • Radiation-sensitive 
  • Part of our unique Genetic Stability Program 
  • Commonly called “BALB scid” 
  • Deficient in mature T and B cells (Nonoyama et al. 1993
  • Innate immunity remains intact 
  • Normal antigen presentation, myeloid development, and NK cell functions 
  • Most mice are devoid of immunoglobulins 
  • Older mice can become "leaky," producing small numbers of mature T and B cells 

B6.129S7-Rag1tm1Mom/J (002216)
  • Commonly called “B6 Rag1” 
  • Produces no mature T or B cells (Mombaerts et al. 1992
  • Innate immunity remains intact 
  • Defective in V(D)J recombination and has no CD3+ or T cell receptor alpha/beta positive cells 
  • Thymocytes are CD4- CD8- and most are IL2R+ 
  • Unlike scid mutants on the same genetic background, is considered “non-leaky” and is radiation-resistant 
J:NU (007850)
  • Commonly called “Outbred Nude” 
  • Segregating genetic background improves hybrid vigor 
  • Homozygous for the nude spontaneous mutation (Foxn1nu (Pantelouris EM. 1973; Flanagan SP. 1966)) 
  • Abnormal hair growth, making engraftment of human or mouse cancer cells, and tumor regression following treatment, easily observable 
  • Athymic: lack T cells and thus incapable of cell-mediated immunity, B cell development is partially defective 
  • Produces normal T cell precursors, and produces mature T cells with time 
  • Responses to thymus-dependent antigens (when detectable) are primarily IgM 
NU/J (002019)
  • Commonly called “Inbred Nude” 
  • Have a uniform genetic background that can improve experimental reproducibility 
  • Homozygous for the nude spontaneous mutation (Foxn1nu(Pantelouris EM. 1973; Flanagan SP. 1966))
  • Abnormal hair growth, making engraftment of human or mouse cancer cells, and tumor regression following treatment, easily observable 
  • Athymic:  lack T cells and thus incapable of cell-mediated immunity, B cell development is partially defective 
  • Produces normal T cell precursors, and produces mature T cells with time 
  • Responses to thymus-dependent antigens (when detectable) are primarily IgM 
  • Challenging breeder: begins to ovulate late (at two and a half months) and stops early (at about four months), but breeds better than Foxn1nu/nu mutants on other inbred genetic backgrounds