NRG Nude Mouse

NRG Nude Mouse Model
The NRG Nude or NOD Rag2 γc “nude” model is a severely immunodeficient inbred strain (NOD background) carrying two knockout (KO) genetic mutations and one natural mutation: the γc KO gene (Interleukin 2 receptor gamma chain, IL2rgTm1), the Rag2 KO gene (recombination activating gene 2), and the natural Nude mutation (Foxn1nu/nu gene).

The Rag2tm1 mutation, commonly referred to as Rag2, is a KO mutation of the gene encoding the recombinase 2 enzyme, which plays a key role in generating T and B lymphocyte receptors. Its absence blocks the development of T and B lymphocytes, leading to immunodeficiency. Mice homozygous for this mutation show a complete lack of peripheral T and B lymphocytes.

The Il2rgtm1 mutation, also known as γc, is a KO mutation of the gene encoding the common gamma chain for several interleukins (IL-2, IL-4, IL-7, IL-9, and IL-15). This gene is essential for the differentiation and function of many hematopoietic cells and is critical for the development of Natural Killer (NK) cells.
The combination of the Rag2tm1 and Il2rgtm1 mutations results in severe immunodeficiency with a complete absence of T, B, and NK cell compartments.

The Nude mutation (Foxn1nu/nu) is an autosomal recessive mutation of the Foxn1 (Forkhead box N1) gene located on chromosome 11, initially identified in a non-inbred mouse colony.
This mutation induces thymic aplasia (complete or partial), resulting in T and B cell immunodeficiency. It is also responsible for a keratinization defect in hair follicles and the epidermis. This defect manifests as a transient fuzz, which, once lost, leads to an almost complete absence of fur.

The NRG Nude strain has also been tested for Sirpα gene polymorphism. The expression of the Sirpα allele (NOD background) on the surface of bone marrow macrophages allows high-affinity binding to human hematopoietic cell CD47 markers. This interaction triggers a “don’t eat me” signal that inhibits mouse macrophages and prevents the phagocytosis of grafted human cells.
This is a notable feature of the NOD background, which offers a significant advantage for human transplantation and xenografting in general.

The NRG Nude strain differs from the NXG strain (NOD-Prkdcscid-Il2rgtm1/Rj) in that it lacks the Prkdcscid mutation, commonly known as “SCID” (Severe Combined Immunodeficiency).
As a result, the NRG strain is more resistant to irradiation, genotoxic compound injection, and stress, making it more stable and sustainable for xenograft applications. The absence of fur also allows for more precise subcutaneous tumor transplantation.

JANVIER LABS obtained the B6 Rag2γc strain (C57BL/6N-Rag2tm1-IL2rgtm1-SirpaNOD/Rj) through homologous recombination (using B6N mouse ES cells), developed at the Centre d’Immunophénomique (Ciphe, Marseille, France) in 2019.

The congenic NRG model was then generated through high-speed backcrossing (N=6) onto a NOD background in 2021.
The Nude gene (Foxn1nu/nu) was subsequently backcrossed onto the NRG model in 2022.

Animals are bred to maintain both the genetic background and the mutations of interest in a homozygous state.
The NRG strain is maintained as an inbred line, and the phenotype is monitored in accordance with the JANVIER LABS GENETIC POLICY®.