Basic Information
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Targeting strategy
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Gene targeting strategy for B-NDG MHC I/II DKO mice plus. The murine B2m and H2-Ab1 gene were knocked out while a fused gene composed of murine B2m and Fcgrt gene was inserted after the signal peptide sequence of murine Fcgrt gene in B-NDG MHC I/II DKO mice plus.
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Protein expression analysis
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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 plus mice and B-NDG MHC I/II DKO mice plus by flow cytometry. Splenocytes were collected from the three mice and analyzed by flow cytometry. Mouse H-2Kb/H-2Db was only detectable in B-NDG mice but not in B-NDG B2m KO plus mice and B-NDG MHC I/II DKO mice plus. Mouse I-Ak was only detectable in B-NDG mice and B-NDG B2m KO plus mice but not in B-NDG MHC I/II DKO mice plus.
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Significantly reduced severity of GvHD induced with human PBMC engraftment in B-NDG MHC I/II DKO mice plus
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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 (Donor1-3) 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.
Comparison of the peripheral blood leukocyte subpopulations in B-NDG mice, B-NDG B2m KO mice plus and B-NDG MHC I/II DKO mice plus after human PBMC engraftment. 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). Blood was collected weekly after engraftment of human PBMC for flow cytometric analysis. The reconstitution levels of all the leukocytes analyzed were similar among the three mice.
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Summary
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Protein expression analysis:
Mouse H-2Kb/H-2Db was only detectable in B-NDG mice but not in B-NDG B2m KO plus mice and B-NDG MHC I/II DKO mice plus. Mouse I-Ak was only detectable in B-NDG mice and B-NDG B2m KO plus mice but not in B-NDG MHC I/II DKO mice plus.
GvHD analysis:
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. B-NDG MHC I/II DKO mice plus are more suitable mouse model for human PBMC engraftment into the immunodeficient mice.
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Poster
