Basic Information

Strain Name
NOD.CB17-Prkdcscid Il2rgtm1Bcgen B2mtm1Bcgen Fcgrttm1(B2m/Fcgrt)Bcgen H2-Ab1tm1Bcgen/Bcgen
Common Name
B-NDG MHC I/II DKO mice plus
Background
B-NDG mice
Catalog number
111895
Related Genes
H2-Ab1: AI845868, Abeta, H-2Ab, H2-Ab, I-Abeta, IAb, Ia-2, Ia2, Rmcs1; B2m: Ly-m11, beta2-m, beta2m; Fcgrt: FcRn
NCBI Gene ID
H2-Ab1: 14961 B2m: 567 Fcgrt: 2217  

Targeting strategy

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.

Protein expression analysis

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.

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 (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.

Summary

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.

Poster

AACR 2023: Development of MHC I/II Knock-Out Immunodeficient Mouse Strains for Alleviating GvHD Induced by Human PBMC Reconstitution

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