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NOG-EXL

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NOG-EXL

Next Generation Severely Immunodeficient NOG-EXL mouse

Next Generation Severely Immunodeficient NOG-EXL mouse
Strain Name NOG-hGM-CSF/hIL-3 Tg (NOG-EXL)
  • You will be required to sign a consent form upon purchase.
  • The use of this mouse strain corresponds to the use of Living Modified Organism (Cartagene Protocol, domestic law). We will send you an information provision form in advance, so please check it and use it according to the rules of each institution.
Development

NOG-EXL mouse was established the following method. Vectors containing human IL-3 or GM-CSF genes downstream of the SRa promoter were microinjected into C57BL/6J-scid mouse embryos and the resulting transgenic mouse was backcrossed to NOG mouse.

Product features of NOG-EXL mouse

The followings are added to the features of the NOG mouse.

  • Increased differentiation of myeloid lineage cells and CD4+ T cells:
    Increased differentiation of myeloid cells such as macrophages, dendritic cells, granulocytes, and mast cells, and CD4+ T cells has been confirmed after human hematopoietic stem cell engraftment.
    It is now possible to conduct research targeting myeloid immune cells, which had been difficult to evaluate using conventional NOG mouse.
  • Useful for research on anti-tumor human plasmacytoid dendritic cells (pDC).
    In September 2020, a paper was published stating that NOG-EXL mouse is useful as a model for studying the functions of in vivo tumor-promoting and anti-tumor human plasmacytoid dendritic cells (pDC).
    Ilona et al., Front. Immunol., 2020
Research Applications
  • Human hematopoietic and immunology related research models, especially differentiation of myeloid cells, evaluation experiments for anti-tumor effects, etc.
  • Human myeloid leukemia tumor-bearing model (AML, CML etc.)
  • Analysis of human innate immune responses
  • In vivo evaluation model for human mast cell-mediated allergic reactions
  • Bone marrow toxicity evaluation experiment for anticancer drugs
Background data

Humanized NOG-EXL mouse

  • Human hematopoietic stem cell (HSC) engrafted models are commonly used.
  • We produce humanized NOG-EXL mouse in Japan and deliver them to our customers.
  • Production will be started after receiving your firm order. We usually ship about 12 weeks after an order is placed.
  • You will be required to sign a consent form upon purchase.
  • The use of this mouse strain corresponds to the use of Living Modified Organism (Cartagene Protocol, domestic law). We will send you an information provision form in advance, so please check it and use it according to the rules of each institution.
Product features of humanized NOG-EXL mouse engrafted with Hematopoietic Stem Cells (HSC)
  • When HSCs are engrafted, myeloid human cells differentiate first. They later differentiate into human T cells and human B cells and engraft.
  • Unlike conventional NOG mouse, enhanced differentiation of myeloid cells such as macrophages, dendritic cells, granulocytes, mast cells and CD4 positive T cells has been confirmed. Differentiation into NK cells is minimal.
  • Humanized mouse has been confirmed to survive for more than 6 months after engraftment. It has been confirmed that the engraftment ratio of human immune cells remains almost unchanged up to 20 weeks after HSCs engraftment.
  • Graft versus host disease (GVHD) caused by human immune cells is not usually seen. Even if cancer cells are transplanted after engraftment of human immune cells, it has been confirmed that engraftment of cancer cells occur in many cases.
  • Compared to conventional humanized NOG mouse, the chimeric ratio of human cells is higher, and macrophages may phagocytize mouse erythrocytes and develop anemia.
  • In the US and EU countries, TACONIC Biosciences Inc. supplies humanized NOG-EXL mouse. The quality standard is the same as that of humanized NOG-EXL mouse supplied in Japan.
Research Applications
  • Human hematopoietic and immunology related research models, especially differentiation of myeloid cells, evaluation experiments for anti-tumor effects, etc.
  • Human myeloid leukemia tumor-bearing model (AML, CML etc.).
  • Analysis of human innate immune responses.
  • In vivo evaluation model for human mast cell-mediated allergic reactions.
  • Bone marrow toxicity evaluation experiment for anticancer drugs.
  • We are providing detailed briefings online regarding the products features of humanized NOG-EXL mouse, the production of humanized NOG-EXL mouse, and experimental protocols for their use. Please feel free to contact us at sales@invivoscience.com.
Background data
Video: NOG-EXL and humanized NOG-EXL

We will introduce the development history of NOG-EXL mouse, the characteristics of NOG-EXL mouse engrafted with HSCs (humanized mouse), and their main research applications.

References

A Comparison of Lymphoid and Myeloid Cells Derived from Human Hematopoietic Stem Cells Xenografted into NOD Derived Mouse Strains.(CD34; NCG; NOG-EXL; NSG; NSG SGM3; humanization; humanized mouse model; lymphoid; myeloid; xenograft.)
Microorganisms. 2023 Jun 10;11(6):1548. doi: 10.3390/microorganisms11061548.PMID: 37375051
Gutierrez-Barbosa H, Medina-Moreno S, Perdomo-Celis F, Davis H, Coronel-Ruiz C, Zapata JC, Chua JV.

Spontaneous early-onset neurodegeneration in the brainstem and spinal cord of NSG, NOG, and NXG mice.(CD34; NOG; NOG-EXL; NSG; NXG; gliosis; neurodegeneration; spontaneous lesion; vacuolation)
Vet Pathol. 2023 May;60(3):374 383. doi: 10.1177/03009858231151403. Epub 2023 Feb 2.
Finesso G, Willis E, Tarrant JC, Lanza M, Sprengers J, Verrelle J, Banerjee E, Hermans E, Assenmacher CA, Radaelli E.

Clinically relevant humanized mouse models of metastatic prostate cancer to evaluate cancer therapies.(humanized mice, NOG, NOG-EXL, Hot Model, Cold Model, metastatic prostate cancer, cancer therapy)
bioRxiv . 2023 Oct 17:2023.10.13.562280. doi: 10.1101/2023.10.13.562280. Preprint.
Kostlan RJ, Phoenix JT, Budreika A, Ferrari MG, Khurana N, Cho JE, Juckette K, McCollum BL, Moskal R, Mannan R, Qiao Y, Griend DJV, Chinnaiyan AM, Kregel S.

PMN-MDSCs modulated by CCL20 from cancer cells promoted breast cancer cell stemness through CXCL2-CXCR2 pathway.(CCL20-modulated PMN-MDSCs, polymorphonuclear myeloid-derived suppressor cells, huNOG-EXL)
Signal Transduct Target Ther 2023 Mar 1;8(1):97. doi: 10.1038/s41392 023 01337 3.
Rui Zhang,Mengxue Dong, Juchuanli Tu, Fengkai Li, Qiaodan Deng, Jiahui Xu, Xueyan He, Jiajun Ding, Jie Xia, Dandan Sheng, Zhaoxia Chang, Wei Ma, Haonan Dong, Yi Zhang, Lixing Zhang, Lu Zhang, Suling Liu

Establishment of a human allergy model using human IL-3/GM-CSF-transgenic NOG mice. (human allergy, NOG-EXL)
J Immunol. 2013 Sep 15;191(6):2890-9. doi: 10.4049/jimmunol.1203543. Epub 2013 Aug 16.
Ryoji Ito, Takeshi Takahashi, Ikumi Katano, Kenji Kawai, Tsutomu Kamisako, Tomoyuki Ogura, Miyuki Ida-Tanaka, Hiroshi Suemizu, Satoshi Nunomura, Chisei Ra, Akio Mori, Sadakazu Aiso, Mamoru Ito

Co-clinical Modeling of the Activity of the BET Inhibitor Mivebresib (ABBV-075) in AML. (AML, NOG-EXL)
In Vivo. 2022 Jul-Aug;36(4):1615-1627. doi: 10.21873/invivo.12872.
Daniel H Albert, Neal C Goodwin, Angela M Davies, Jenny Rowe, Gerold Feuer, Michael Boyiadzis, Kathleen A Dorritie, Maria Mancini, Regina Gandour-Edwards, Brian A Jonas, Gautam Borthakur, Ibrahim Aldoss, David A Rizzieri, Olatoyosi Odenike, Thomas Prebet, Sanjana Singh, Relja Popovic, Y U Shen, Keith F McDaniel, Warren M Kati, Dimple A Modi, Monica Motwani, Johannes E Wolff, David J Frost

Eliminating chronic myeloid leukemia stem cells by IRAK1/4 inhibitors.(CML-LSCs, NOG-EXL)
Nature Communications volume 13, Article number: 271 (2022)
Yosuke Tanaka, Reina Takeda, Tsuyoshi Fukushima, Keiko Mikami, Shun Tsuchiya, Moe Tamura, Keito Adachi, Terumasa Umemoto, Shuhei Asada, Naoki Watanabe, Soji Morishita, Misa Imai, Masayoshi Nagata, Marito Araki, Hitoshi Takizawa, Tomofusa Fukuyama, Chrystelle Lamagna, Esteban S. Masuda, Ryoji Ito, Susumu Goyama, Norio Komatsu, Tomoiku Takaku & Toshio Kitamura

Transplantation of insulin-producing cells derived from human mesenchymal stromal/stem cells into diabetic humanized mice. (hAT-MSCs, NOG-EXL)
Stem Cell Res Ther. 2022 Jul 26;13(1):350. doi: 10.1186/s13287-022-03048-y.
Ghoneim MA, Gabr MM, Refaie AF, El-Halawani SM, Al-Issawi MM, Elbassiouny BL, Kader MAAE, Ismail AM, Zidan MF, Karras MS, Magar RW, Khater SM, Ashamallah SA, Zakaria MM, Kloc M.

Bovine β-lactoglobulin-induced passive systemic anaphylaxis model using humanized NOG hIL-3/hGM-CSF transgenic mice. (passive systemic anaphylaxis model, NOG-EXL )
Int Immunol. 2021 Mar 1;33(3):183-189. doi: 10.1093/intimm/dxaa067.
Ito R, Katano I, Otsuka I, Takahashi T, Suemizu H, Ito M, Simons PJ.

The Tumor Milieu Promotes Functional Human Tumor-Resident Plasmacytoid Dendritic Cells in Humanized Mouse Models. (pDC, humanized mice, NOG-EXL)
Front Immunol. 2020 Sep 8;11:2082. doi:10.3389/fimmu.2020.02082. eCollection 2020.
Maser IP, Hoves S, Bayer C, Heidkamp G, Nimmerjahn F, Eckmann J, Ries CH.

Establishment of Humanized Mice from Peripheral Blood Mononuclear Cells or Cord Blood CD34+ Hematopoietic Stem Cells for Immune-Oncology Studies Evaluating New Therapeutic Agents. (humanized mice, NOG-EXL, Immune oncology, PDX)
Curr Protoc Pharmacol. 2020 Jun;89(1):e77. doi: 10.1002/cpph.77.
Ghoneim MA, Gabr MM, Refaie AF, El-Halawani SM, Al-Issawi MM, Elbassiouny BL, Kader MAAE, Ismail AM, Zidan MF, Karras MS, Magar RW, Khater SM, Ashamallah SA, Zakaria MM, Kloc M.

HIV Replication in Humanized IL-3/GM-CSF-Transgenic NOG Mice. (humanized mice, NOG-EXL, HIV)
Pathogens. 2019 Mar 12;8(1):33. doi: 10.3390/pathogens8010033.
Perdomo-Celis F, Medina-Moreno S, Davis H, Bryant J, Zapata JC.

BLT-Immune Humanized Mice as a Model for Nivolumab-Induced Immune-Mediated Adverse Events: Comparison of the NOG and NOG-EXL Strains. (NOG, NOG-EXL)
Toxicol Sci. 2019 May 1;169(1):194-208. doi: 10.1093/toxsci/kfz045.
Weaver JL, Zadrozny LM, Gabrielson K, Semple KM, Shea KI, Howard KE.