huNOG-EXL mice have extended lifespan compared to competing models

Survival curve for huNOG-EXL mice across 23 donors (n=5-9 per donor), generated in the Taconic Biosciences humanization core during 2022-2023. The huNOG-EXL has the longest demonstrated lifespan compared to competing models; this varies by donor and can be impacted by environmental and experimental factors. All myeloid-supportive HIS mice have limited lifespans due to a range of outcomes including anemia, thrombocytopenia and myeloid cell hyperactivation syndrome (Internal Taconic data).

 

Kinetics of Human Immune Cell Reconstitution in huNOG-EXL (Peripheral Blood)

huNOG-EXL mice support high levels of human immune cells in peripheral blood (chimerism) and develop both myeloid and lymphoid cells. huNOG-EXL EA mice are shipped shortly after engraftment, prior to reconstitution of significant numbers of human immune cells in peripheral blood. huNOG-EXL SA mice are shipped after a QC step to confirm that each mouse has ≥25% human cells in peripheral blood at 10 weeks post-engraftment.

How Taconic Addresses HIS Mouse Variability

Donor characteristics impact human immune system reconstitution in huNOG-EXL mice, including chimerism levels and frequencies of specific human immune cell types. As shown in the graph of huNOG-EXL SA models below, engraftment lots for which the mean falls below Taconic's 25% chimerism threshold are disqualified from sale (shown in red). For lots with a mean above the threshold (shown in blue), any individual animals in the lot which score below 25% are disqualified from sale. For huNOG-EXL EA, Taconic selects donors that have previously been validated to reduce the risk of lot failure. Taconic's Field Application Scientists can help you design a successful study plan which appropriately accounts for both inter- and intra-donor variation in HIS mice and select the right huNOG-EXL version for your research.

huNOG-EXL EA Mice Are Engrafted Using Donor Cells with Proven Engraftment Success

In order to determine the level of engraftment in huNOG-EXL models, HSCs from the same donor were engrafted twice, on separate days, to generate two lots of huNOG-EXL mice per donor. The ability of a donor to produce lots where most mice either met or failed the QC threshold of ≥25% chimerism was replicated between duplicate lots, with one exception in this test set. To generate huNOG-EXL EA mice, Taconic chooses donors with proven engraftment success in order to reduce the risk of lot failure.

Hematopoiesis and Humanized Immune System Mice

Both huNOG-EXL SA and EA models develop human myeloid and lymphoid lineages.