| Strain Name |
NOD.CB17-PrkdcscidIL2rgtm1B2mtm1Fcgrttm1(B2m/Fcgrt)H2-Ab1tm1/Bcgen |
Common Name |
B-NDG MHC I/II DKO mice plus |
| Background | B-NDG mice | Catalog number | 111895 |
| Aliases |
H2-Ab1: AI845868, Abeta, H-2Ab, H2-Ab, I-Abeta, IAb, Ia-2, Ia2, Rmcs1; |
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Strain specific H-2Kb/H-2Db (MHC-I) and I-Ak (MHC-II) expression analysis in B-NDG mice, B-NDG B2m KO mice plus and B-NDG MHC I/II DKO mice plus by flow cytometry. Splenocytes were collected from the three strains of mice and analyzed by flow cytometry. Results indicated that mouse H-2Kb/H-2Db were only detectable in B-NDG mice but not in B-NDG B2m KO mice plus and B-NDG MHC I/II DKO mice plus. Mouse I-Ak was only detectable in B-NDG mice and B-NDG B2m KO mice plus but not in B-NDG MHC I/II DKO mice plus. This indicates that MHC I/II molecules in B-NDG MHC I/II DKO plus mice have been successfully knocked out.
Significantly reduced severity of GvHD induced with human PBMC engraftment in B-NDG MHC I/II DKO mice plus
Comparison of the severity of GvHD induced with human PBMC engraftment in B-NDG mice, B-NDG B2m KO mice plus and B-NDG MHC I/II DKO mice plus.
Five weeks old of female B-NDG mice, B-NDG B2m KO mice plus and B-NDG MHC I/II DKO mice plus were respectively engrafted intravenously with human PBMCs (5 × 106) from three healthy donors (Donor 1-3) on day 0 (n=5). A. Survival rates of the mice were analyzed with Kaplan Meier survival curves. B. Body weight changes. C. Clinical signs of GvHD were scored twice a week. Results showed that MHC I/II double knocked-out in B-NDG MHC I/II DKO mice plus can significantly extend the life span and reduced the GvHD induced with human PBMC engraftment when compared that in B-NDG mice or in B-NDG B2m KO mice plus. Therefore B-NDG MHC I/II DKO mice plus are more suitable mouse model for human PBMC engraftment into the immunodeficient mice. Values were expressed as mean ± SEM.
High reconstitution level of human PBMCs
Comparison of reconstitution levels of human PBMCs among B-NDG mice, B-NDG B2m KO mice plus and B-NDG MHC I/II DKO mice plus.
B-NDG mice, B-NDG B2m KO plus mice, and B-NDG MHC I/II DKO plus mice were respectively intravenously injected with human PBMCs (5E6) derived from three healthy donors (donor1-3) on day 0 (n = 5, female, 5 weeks old). Peripheral blood was taken weekly to analyze the reconstitution level of human immune cells. The experiment was ended 90 days after reconstitution. The results showed that 2 weeks after hPBMCs reconstitution in B-NDG MHC I/II DKO plus mice, the proportion of reconstituted human CD45+ cells was more than 50%, but slightly lower than the levels in B-NDG mice and B-NDG B2m KO plus mice. the main reconstituted cells were human T cells, and the number of this cell was slightly lower than that in B-NDG mice and B-NDG B2m KO plus mice (data not shown). But the proportion of the cells was similar. Donor 3-derived human PBMCs showed the highest reconstitution levels (human CD45+ cells, CD4+ T cells). Combined with the results of GvHD, it was demonstrated that deletion of MHCI/II molecules in B-NDG MHC I/II DKO plus mice significantly delayed GvHD induced by human PBMC reconstitution and significantly reduced the severity of GvHD. Human PBMCs from different donor sources had an effect on reconstitution, but the influence was much lower than that on B-NDG mice and B-NDG B2m KO plus mice. Reconstitution levels in B-NDG MHC I/II DKO plus mice, although slightly lower than the other two mice, remained high. Regardless of the mice, the higher the reconstitution level of human T cells, especially human CD4+ T cells, the more severe the GvHD. Thus, B-NDG MHC I/II DKO mice plus are a more suitable immunodeficient mouse model for reconstitution of the human immune system using human PBMCs.
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