NXG-HIS Humanized Mouse
The reference model for immunotherapeutics development
Inbred transgenic mouse, GEMM
JANVIER LABS, in 2021
Colour and related genotype:
CD34 from blood cord.
Description of our model and application areas
The NXG-HIS is the humanized model corresponding to the NXG or NOD Xenograft Gamma strain which is an inbred strain model (on the NOD background) with 2 mutations of interest, (Prkdcscid and IL2rgTm1). The combination of these mutations induces a severe immunodeficiency with an absence of T, B and NK lymphocyte compartments. NXG mouse is therefore genetically similar to NSG, NcG, NOG, etc. (NOD SCID Gamma). The NXG strain also carries the NOD polymorphism of the Sirpα gene.
The Sirpα protein is expressed on the surface of macrophages. The NOD Sirpα allele allows high affinity binding to the CD47 ligand expressed by human hematopoietic cells. This interaction induces a “don’t eat me” signal that blocks murine macrophage activations and prevents phagocytosis of transplanted human cells.
The NOD Sirpα allele is a key feature of the NOD background which gives an advantage for human transplantation and xenografting in general.
Main application and research fields
The humanization protocol has been standardized in JANVIER LABS’ laboratories. The depletion of the bone marrow is carried out by injection of busulfan the day before the injection of human cells CD34+. Flow cytometry analyses are performed to measure the rate of humanization 14 weeks after injection. Animals are available and can be used for preclinical studies, with SOPF status and for a humanization rate (%CD45+ human) greater than or equal to 25% minimum.
The growth curve represents an average which reflects the weight variation of the strain measured between 3 and 12 weeks for males and females.
NXG-HIS mice growth curve
Female NXG-HIS growth curve
Quality control of the humanization rate
Quality control allows to measure the relative humanization rate of humanized mice in the peripheral blood. The standardization of quality control is performed by flow cytometry of the different human populations: hematopoietic, lymphoid and myeloid. Each NXG-HIS is tested and analysed before sending and use. Analyses of the rate of humanization (absolute number and percentage) in the first weeks show a stability of at least 22 weeks post-injection.
NXG-HIS mice are produced with SOPF status. Each batch provided is supplied with a list showing the animal repartition according to the different CD34+ donors.
Flow cytometry analysis, humanization level (100 x %hCD45+) / (%mCD45+ + %hCD45+)
Kinetics of humanization by CD45
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