FcResolv hIL-15 NOG Mouse Model

NOD Background

  • Model #
  • Genotype
  • Nomenclature
  • 19220-F
    ko/ko;ko/ko;sp/sp;ko/ko;tg/wt
    NOD.Cg-Fcgr2btm1Ttk Fcer1gtm1Rav Prkdcscid Il2rgtm1Sug Tg(CMV-IL2/IL15)1-1Jic/JicTac
  • 19220-M
    ko/ko;ko/ko;sp/sp;ko/y;tg/wt
    NOD.Cg-Fcgr2btm1Ttk Fcer1gtm1Rav Prkdcscid Il2rgtm1Sug Tg(CMV-IL2/IL15)1-1Jic/JicTac
  • The FcResolv hIL-15 NOG is a super immunodeficient NOG mouse that expresses human IL-15 to support engraftment of human NK cells and which has a further reduction in residual murine immune activity via ablation of mouse Fc gamma receptors (FcγRs) in order to reduce experimental confounders.
  • Murine FcγRs can confound experiments in several ways, leading to false positive or negative results. Removing murine FcγRs provides improved accuracy for efficacy assessment of antibody-based therapies which include an Fc domain.
  • Lacks all murine FcγRs, including the FcγRI, IIB, III and IV types, along with the high affinity FcεRI receptor. The low affinity FcεRII receptor remains present.
  • Supports engraftment of human NK cells following engraftment with CD56+ NK cells derived from PBMCs and can be used in a similar fashion to the hIL-15 NOG.
  • The FcResolv hIL-15 NOG mouse is optimized for engraftment of isolated primary human NK cells, immortalized human NK cell lines or human NK cell therapies. Humanization with HSCs is not recommended in this model. While HSC engraftment results in strong proliferation of NK cells, lifespan post-differentiation is very limited. Humanization of this strain with PBMCs is not recommended as an optimal model to study human NK cells, but may be of interest for GvHD applications.
  • Useful for efficacy studies involving antibody therapeutics with antibody-dependent cell cytotoxicity (ADCC) mechanism of action.
  • Applications in research involving cancer, infectious disease, immunology, regenerative medicine, and human immune system engraftment.

Orders by weight: Taconic cannot accept orders by weight for this model. Please note that shipments may contain animals with a larger weight variation.

Small image of Infographic Download the Taconic Biosciences' Infographic:
FcResolv™ NOG Mouse Models Are Specifically Designed to Reduce False Positives and Negatives Mediated by Mouse Fc Gamma Receptors in Studies Using Antibody-Based Drugs



See how the FcResolv hIL-15 NOG mouse reduces experimental confounders.

Origin:

The FcResolv hIL-15 NOG mouse was developed by Takeshi Takahashi of the Central Institute for Experimental Animals (CIEA) in Japan. The Fcer1gtm1Rav mutation was developed in the laboratory of J.V. Ravetch, Sloan-Kettering Institute. The Fcgr2btm1Ttk mutation was developed in the laboratory of T. Takai of Okayama University. These two mutations were backcrossed onto the CIEA NOG mouse®, and the resulting FcResolv NOG mouse was crossed to the hIL-15 NOG to generate the FcResolv hIL-15 NOG. Taconic received stock in 2021, and the line was derived through embryo transfer. The mice are maintained by breeding females homozygous for the Fcer1gtm1Rav, Fcgr2btm1Ttk, Prkdcscid and Il2rgtm1Sug mutant alleles with males that are homozygous for the Fcer1gtm1Rav, Fcgr2btm1Ttk, Prkdcscid alleles and hemizygous for the Il2rgtm1Sug mutant allele and hIL-15 transgene or females homozygous for the Fcer1gtm1Rav, Fcgr2btm1Ttk, Prkdcscid and Il2rgtm1Sug mutant alleles and hemizygous for the hIL-15 transgene by males homozygous for the Fcer1gtm1Rav, Fcgr2btm1Ttk, Prkdcscid alleles and hemizygous for the Il2rgtm1Sug mutant allele.


Availability:

Available now*

*Please note that advanced order placement is encouraged for male mice. Ordering 4 or more weeks prior to the desired shipping date is recommended when requesting males older than 3-weeks of age.

Color:

Albino

Species:

Mouse

Initial Publication:

Katano I, Ito R, Kawai K, Takahashi T. Improved Detection of in vivo Human NK Cell-Mediated Antibody-Dependent Cellular Cytotoxicity Using a Novel NOG-FcγR-Deficient Human IL-15 Transgenic Mouse. Front Immunol. 2020 Oct 7;11:532684.



Nonprofit users (excluding users at nonprofit foundations which are affiliated with a for-profit entity): For internal research purposes, the CIEA NOG mouse® Conditions of Use for nonprofit users apply. If you wish to perform sponsored research or fee-for-service contract research using the CIEA NOG mouse®, please inquire for access conditions

For-profit users and users at foundations which are affiliated with for-profit entities: The CIEA NOG mouse® Conditions of Use for for-profit users apply.

Does your research require the use of neonates? Please contact us for more information on neonate access options.

The CIEA NOG mouse® is produced and distributed under license rights to the following patents and trademarks:
  • Japanese Patent No. 3,753,321
  • US Patent No. 7,145,055; 5,464,764; 5,487,992; 5,627,059; 5,631,153; 5,789,215; 6,204,061; 6,653,113; 6,689,610
    EP Patent No. 1,338,198
  • Japanese Trademark Reg. No. 4,823,423
  • US Trademark Reg. No. 3,118,040
  • EU Trademark Reg. No. 3,736,758

FcResolv hIL-15 NOG PERMITS SPECIFIC DETECTION OF EFFECTS MEDIATED THROUGH HUMAN NK CELLS

FcResolv hIL-15 NOG mice specifically identify anti-tumor effects mediated by human cells. In hIL-15 NOG mice, strong anti-tumor activity against Daudi cells was seen with rituximab, regardless of whether human NK cells were present, indicating a strong effect mediated through murine innate cells. While rituximab alone showed some effect in FcResolv hIL-15 NOG mice, rituximab plus human NK cells showed the largest decrease in Daudi cell dissemination compared to saline or saline + human NK cell controls. It is thus possible to specifically detect human NK cell-mediated ADCC in the FcResolv hIL-15 NOG strain. A) Representative images of immunohistochemistry of kidneys. B) Daudi cell dissemination was measured via immunohistochemistry using automated image analysis of kidney sections.FcResolv hIL-15 NOG mice specifically identify anti-tumor effects mediated by human cells. In hIL-15 NOG mice, strong anti-tumor activity against Daudi cells was seen with rituximab, regardless of whether human NK cells were present, indicating a strong effect mediated through murine innate cells. While rituximab alone showed some effect in FcResolv hIL-15 NOG mice, rituximab plus human NK cells showed the largest decrease in Daudi cell dissemination compared to saline or saline + human NK cell controls. It is thus possible to specifically detect human NK cell-mediated ADCC in the FcResolv hIL-15 NOG strain. A) Representative images of immunohistochemistry of kidneys. B) Daudi cell dissemination was measured via immunohistochemistry using automated image analysis of kidney sections.
Figure 1: FcResolv hIL-15 NOG mice specifically identify anti-tumor effects mediated by human cells. In hIL-15 NOG mice, strong anti-tumor activity against Daudi cells was seen with rituximab, regardless of whether human NK cells were present, indicating a strong effect mediated through murine innate cells. While rituximab alone showed some effect in FcResolv hIL-15 NOG mice, rituximab plus human NK cells showed the largest decrease in Daudi cell dissemination compared to saline or saline + human NK cell controls. It is thus possible to specifically detect human NK cell-mediated ADCC in the FcResolv hIL-15 NOG strain. A) Representative images of immunohistochemistry of kidneys. B) Daudi cell dissemination was measured via immunohistochemistry using automated image analysis of kidney sections. From Katano 2020.

FcResolv hIL-15 NOG SUPPORTS ENGRAFTMENT OF HUMAN NK CELLS

hIL-15 NOG mice support the engraftment of expanded human NK cells with engraftment levels and persistence similar to the base hIL-15 NOG mouse.
Figure 2: FcResolv hIL-15 NOG mice support the engraftment of expanded human NK cells with engraftment levels and persistence similar to the base hIL-15 NOG mouse. From Katano 2020.
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