These NSG-MHC I/II DKO mice are also called NSG-(KbDb)null (IA)null or NSG-(Kb Db)null (IAnull) in Brehm et al. 2019 FASEB J [PMID:30383447]. These mice are NOD.scid;IL2rg-deficient (NSG) animals also containing null targeted mutations for mouse MHC class I genes (H2-K1 and H2-D1) and a TALEN-made null mutation for the mouse class II gene (H2-Ab1 [I-A]) - making them an MHC I/II double knock-out. These NSG-MHC I/II DKO mice combine the features of the severe combined immune deficiency mutation or scid (B and T cell deficiency), IL2 receptor gamma chain deficiency (NK cell deficiency), MHC class I molecule deficiency (H2-K and D), and MHC class II molecule deficiency (IA). Mice homozygous for the five mutations are viable, normal in size and do not display any gross physical or behavioral abnormalities. These mice exhibit a significantly delayed onset of xenogeneic GvHD compared to NSG mice. The rate and severity of onset is highly dependent on preparatory irradiation dose (or absence), specific donor used, and cell dose injected. Each PBMC donor requires a pilot engraftment using more than one cell dose to determine the overall engraftment characteristics. Once established, these engraftment characteristics are highly reproducible. At JAX, the survival of non-irradiated mice injected with 10 x 106 human peripheral blood mononuclear cells (PBMC) is greater than 100 days, with 13/15 of mice exhibiting no symptoms of GVHD for up to 125 days. Because this strain carries a null mutation in the MHC class I H2-Ab1 gene rather than &beta;-2M, IgG clearance is similar to that observed in the NSG model. This strain may be useful to study human immunity in the absence of GVHD and to evaluate antibody-based therapeutics.
 Stock No. 025216 may be prone to aggressive behavior, including whisker picking, barbering and biting [June 2025]. To help mitigate this, we suggest that, upon receiving the mice, researchers add enrichment items (e.g., a Shepherd Shack) and reduce housing density.

Notice regarding distribution of this strain.

Use of MICE by companies or for-profit entities requires a no-fee JAX Leap License prior to shipping.

NSG-MHC I/II DKO mutant mice combine the features of the severe combined immune deficiency mutation (scid), IL2 receptor gamma chain deficiency, MHC class I molecule deficiency (H2-K and D), and MHC class II molecule deficiency (IA) and exhibit a significant delay in the onset of graft versus host disease (GVHD). They provide a model useful to study in vivo mechanisms of xenogeneic GVHD and to rapidly assess therapeutic agents. These NSG-MHC I/II DKO mice are also called NSG-(KbDb)null (IA)null or NSG-(Kb Db)null (IAnull) in Brehm et al. 2019 FASEB J [PMID:30383447]. CD34+ humanized NSG-MHC I/II DKO (Stock No. 702516) and PBMC humanized NSG-MHC I/II DKO (Stock No. 742516) mice can be ordered on our <a href="https://www.jax.org/jax-mice-and-services/preclinical-research-services/humanized-mice/humanized-mice-form">humanized mouse order form</a>.

Homozygous for Prkdc<scid>, Homozygous for H2-K1<b-tm1Bpe>, Homozygous for H2-Ab1<g7-em1Mvw>, Homozygous for H2-D1<b-tm1Bpe>, Homozygous for Il2rg<tm1Wjl>

Homozygous for Prkdc<scid>, Homozygous for H2-K1<b-tm1Bpe>, Homozygous for H2-Ab1<g7-em1Mvw>, Homozygous for H2-D1<b-tm1Bpe>, Hemizygous for Il2rg<tm1Wjl>