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B2m-NOG

B2m-NOG
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NOD Background

  • Model #
  • Genotype
  • Nomenclature
  • 14957-F
    ko/ko;sp/sp;ko/ko
    NOD.Cg-B2mem1Tac Prkdcscid Il2rgtm1Sug/JicTac
  • 14957-M
    ko/ko;sp/sp;ko/y
    NOD.Cg-B2mem1Tac Prkdcscid Il2rgtm1Sug/JicTac

  • The B2m-NOG is an immunodeficient CIEA NOG mouse® with an additional knockout of the B2m gene which disrupts MHC class I antigen presentation.
  • B2m-NOG mice can successfully engraft human PBMCs and tumors.
  • Compared to NOG, B2m-NOG mice have markedly delayed GvHD onset after human PBMC engraftment, providing an expanded study window (8+ weeks). This vastly increases the utility of the model in immuno-oncology experiments.
  • B2m-NOG has reduced efficiency of human PBMC engraftment relative to NOG as well as a CD4+ bias that increases over time in engrafted peripheral blood T cells (see data section).
  • Available engrafted with human PBMCs as huPBMC-B2m-NOG.
Orders by weight: Taconic cannot accept orders by weight for this model. Please note that shipments may contain animals with a larger weight variation.

Origin:

The CIEA NOG mouse® was developed by Mamoru Ito of the Central Institute for Experimental Animals (CIEA) in Japan. The Prkdcscid mutation was identified by Mel Bosma of the Fox Chase Cancer Center in a C.B-17 congenic mouse population. This mutation was backcrossed onto the NOD/ShiJic strain at CIEA for at least eight generations. The Il2rg targeted mutation was developed by Dr. Kazuo Sugamura of Tohoku University by targeting the gene in ES cells derived from a 129 strain. Targeted ES cells were injected into C57BL/6 blastocysts. Resultant chimeras were backcrossed onto the C57BL/6JJic background for at least eight generations. The CIEA NOG mouse® was developed by backcrossing the C57BL/6JJic-Il2rg line to the NOD/ShiJic-Prkdcscid line for a total of eight generations. The B2m gene was knocked out via CRISPR-mediated knock-in of a nonsense mutation into exon 1. This mutation was made directly in the NOG strain.

Availability:

Available now in typical study quantities.

Color:

Albino

Species:

Mouse

Initial Publication:

Verma, B.; Ruggeri, B.; Dubé, P.; Volden, P.; Wesa, A. Unique Immunodeficient Murine Host Strains Impact Expansion and Engraftment of T cells in PBMC Humanized Mice. New York Academy of Sciences’ Frontiers in Cancer Immunotherapy. May 14-15, 2019; New York, NY.


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.

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
Conditions of Use specific to models generated using CRISPR/Cas9
This Model was generated using CRISPR/Cas9 technology. Taconic uses CRISPR/Cas9 technology to generate and/or distribute gene-edited models under licenses from The Broad Institute, Inc., the Massachusetts Institute of Technology, the President and Fellows of Harvard College, the University of Iowa Research Foundation and ERS Genomics. View the full list of licensed patents:
  • This Model and biological materials derived from it may only be used for purchasers' internal research purposes in the Field, unless purchaser otherwise has rights from the Broad covering such use. "Field" means use as a research tool for research purposes, and expressly excludes any (a) clinical use, (b) human, veterinary, livestock or agricultural use, or (c) manufacture, distribution, sale, promotion, use or other exploitation as a testing service, therapeutic or diagnostic for humans or animals.
  • The Models and biological materials derived from them will not be sold or used to perform services for third parties (unless purchaser is acting on behalf of a third party to which they have communicated these Conditions of Use and which third party has accepted these Conditions of Use), or otherwise used for commercial purposes.
  • Purchasers will only use the Models and biological materials derived from them in compliance with all applicable laws and regulations, including applicable human health and animal welfare laws and regulations.
  • Each non-profit purchaser agrees that it, and not Taconic's licensors, shall be responsible for any liability, damage, loss or expense arising out of or related to purchaser's use of the purchased Models and any biological materials derived from them , including any breach of the Label License "Conditions of Use for Taconic Transgenic Models" by purchaser.
  • Each for-profit purchaser further agrees that it shall indemnify, defend and hold harmless Taconic's licensors against any liability, damage, loss, or expense (including without limitation reasonable attorneys' fees and expenses) incurred by or imposed upon any of Taconic's licensors in connection with any claims, suits, investigations, actions, demands or judgments arising out of or related to purchaser's use of the purchased Models and any biological materials derived from them.
  • Each purchaser acknowledges that the purchased Models and any biological materials derived from them and its use may be the subject of one or more issued patents and/or pending patent applications owned by Taconic's licensors, and the purchase of the Models does not convey a license under any claims in the foregoing patents or patent applications.

B2m-NOG mice successfully engraft human PBMCs

PBMC engraftment in NOG-B2m

B2m-NOG mice at 6-11 weeks of age were engrafted with varying doses of human PBMCs via tail vein injection. Engraftment was assessed weekly by flow cytometry of peripheral blood samples and is expressed as human CD3/mouse CD45.

B2m-NOG mice have extended survival following human PBMC engraftment

GvHD-free survival of PBMC engrafted mouse strains

NOG and B2m-NOG mice at 6-11 weeks of age were engrafted with 1 x 107 human PBMCs from a single donor via tail vein injection. Mice were monitored for signs of xenogeneic Graft vs. Host Disease for up to 8 weeks post engraftment. Data is shown in the Kaplan-Meier survival curve to represent proportion of mice exhibiting xenogeneic GvHD-free survival for the study duration by group (N=6/cohort). (P<0.001, Log rank Mantel-Cox test).

T cell subsets in B2m-NOG mice engrafted with human PBMCs

B2m-NOG mice at 6-11 weeks of age were engrafted with 1 x 107 human PBMCs from a single donor via tail vein injection. Peripheral blood samples were collected weekly and immunophenotyped for T cells (CD3) and T cell subsets (CD4, CD8) to assess of T cell subset development and kinetics. Flow cytometry was used to assess CD4 and CD8 T cell subsets across groups. Results represent the average ± SD (N=5-6/cohort).
All data adapted from Verma et al. 2019.