B-NDG MHC I/II DKO mice plus

Basic Information

Strain Name
NOD.CB17-PrkdcscidIL2rgtm1B2mtm1Fcgrttm1(B2m/Fcgrt)H2-Ab1tm1/Bcgen
Common Name
B-NDG B2m plus/H2-Ab1 KO mice
Background
B-NDG
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

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.

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.