B:Biocytogen; N:NOD background; D:DNAPK（Prkdc）null;G:IL2rg knockout.
B-NDG mice are mice with NOD genetic background and Prkdc and IL2rg double gene knockout. They are internationally accepted mouse modl with the highest degree of immunodeficiency, and they are suitable for human cells or tissue transplantation.
NOD (non-obese diabetes) genetic background: spontaneous type-I diabetes; macrophages have weak human cell cytophagy; innate immune system functions such as complement system and dendritic cells are reduced.
Prkdc(scid): Prkdc (protein kinase DNA-activated catalytic) gene mutation; functional T cells and B cells of mice are lost; lymphocytes are reduced; manifested to have severe combined immune deficiency (scid) of cellular immunity and humoral immunity.
IL2rgnull: the gamma chain of Interleukin-2 receptor (IL-2R γc, also called as CD132) is on the mouse X chromosome, and is the common receptor subunit of cytokines IL2, IL-4, IL-7, IL-9, IL-15 and IL-21 with significant immune functions; after the gene is knocked out, mouse immunity function is greatly weakened, in particular activities of NK cells, which are nearly lost.
B-NDG mice: comprehensive background features of NOD-SCID-IL2rg, with severe immunodeficiency phenotype; no mature T cells, B cells or functional NK cells; deficient in cytokine signaling capacity. Very suitable for transplantation and growth of human hematopoietic stem cells and peripheral blood mononuclear cells.
|Mouse model with currently the highest immunodeficiency degree in the world||Human-derived cells or tissues transplantation|
|Longer lifespan than that of NOD-scid mice; 1.5 years on average||Tumor and tumor stem cell study|
|Almost no rejection of human-derived cells and tissues||ES and iPS cell study|
|Some cells can form tumors, depending on cell lines or cell types||Hematopoiesis and immunology study|
|No B lymphocyte leakage||Human disease infection model study|
|New humanized animal model study|
Preliminary phenotypic analysis
Fig.1 Complete loss of T, B and NK cells of B-NDG mice.
Spleen cells of C57BL/6, BALB/c, NOD-scid and B-NDG mice were isolated, and compositions of T, B and NK cells were characterized using flow cytometry and statistically compared.
|Fig.2 Successful engraftment of hPBMCs (human peripheral blood mononuclear cells) in B-NDG mice. Twenty-four days after injecting 5X106 of human peripheral blood mononuclear cells (hPBMCs) into the tail vein of B-NDG mice, blood was isolated and subjected to FACS analysis to detect ratio of hCD45+ to mCD45+. Similar results were obtained for all three B-NDG mice.|
Fig.3 Successful engraftment of Raji cells in B-NDG mice
The same amount (5X106) of Raji cells were injected into B-NDG, NOD-scid and BALB/c Nude mice. We recorded and analyzed the following indicators in the mice at different time points.
Fig.4: B-NDG is a better choice for modeling in comparison to CB17-scid mice,
C. Comparison of tumor take rate of gastric cancer samples in CB17-scid mice and B-NDG mice bodies.