B6RGS Mouse

The B6RGS mouse is a severely immunodeficient mouse with two Knock Out (KO) genetic mutations: the γc KO gene (Interleukin 2 receptor gamma chain, IL2rgtm1) and the Rag2
KO (Rag2tm1 mutation) gene.

The Rag2tm1 mutation commonly called Rag2 is a KO mutation of the gene coding for the 2 recombinase enzyme that plays a key role in producing T and B cell receptors. This lack leads to an immune deficiency. Homozygous mice for this mutation appear with a total lack of peripheral T and B lymphocyte cells.

The IL2rgtm1 mutant called γc is a KO mutation of the gene coding for the γc gamma chain that is common (in particular) to interleukins (IL-2, IL-4, IL-7, IL-9 and IL-15). This gene is necessary for the differentiation and the function of numerous hematopoietic cells with a full impact on the development of Natural Killer cells (NK).
The combination of both mutations Rag2tm1-IL2rgtm1 on a B6 background leads to a severe immunodeficiency with no T, B and NK cells.

The B6RGS mouse carries the sirpa gene from the NOD genetic background. Expression of the sirpa protein (NOD alleles) on the surface of bone marrow macrophages allows high affinity binding with the CD47 markers of human hematopoietic cells. This binding induces a “don’t eat me” signal blocking murine macrophages and preventing phagocytosis of transplanted human cells. This is a notable feature of the NOD genetic background which gives it an advantage in human transplantation and xenografting in general. JANVIER LABS obtained the B6 Rag2γc (C57BL/6N-Rag2tm1-IL2rgtm1/Rj) through a homologous recombination (ES cells from B6N mice), developed at the Center of Immunophenomics (Ciphe, Marseille, France) in 2019.

The sirpa gene has been identified by PCR and extracted from the NOD fund by crossing on B6 funds. The B6RGS have been backrossed (>10 generations) in 2021 to the B6 background. The B6 Rag2 strain is bred in an inbred manner and the phenotype is controlled according to the JANVIER LABS GENETIC POLICY®.