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hIL-15 NXG Mouse

Immunodeficient Mouse

Model characteristics

Strain name:

NOD-Prkdcscid-IL2rgtm1-Il15em1(IL15)/Rj

Modèle Type:

Inbred mutated mouse


Origin:

JANVIER LABS, in 2019

Colour and related genotype:

Albino mouse

Performance de reproduction :


In vivo

Description of our model and application areas

The hIL-15 NXG model was developed by replacing the murine Il15 gene with the human IL15 gene in the NXG strain.

Key Mutations:

  • Prkdcscid: This mutation disrupts the development of T and B cells, resulting in their complete absence.
  • Il2rgtm1: A knockout of the gene encoding the IL-2 receptor subunit gamma, which is essential for several interleukins (IL-2, IL-4, IL-7, IL-9, IL-15). This mutation results in the absence of NK cells.

These combined mutations lead to severe immunodeficiency with the absence of T, B, and NK cells. Additionally, the hIL-15 NXG strain expresses the NOD variant of the Sirpa gene, enhancing cross-recognition between murine macrophages and human cells, thereby reducing the phagocytosis of transplanted human cells.

  • Il15em1(IL15): The murine Il15 gene was replaced with the human IL15 gene. IL-15 is a cytokine crucial for the development, survival, and activation of NK cells and memory T cells, playing a vital role in immune response regulation.

hIL-15 Feature: This model exhibits physiological hIL-15 expression, with a resting serum level of approximately 80 pg/mL, rising to 400 pg/mL in response to inflammation and immune activation. This response closely mirrors human physiological conditions compared to other strains.

Model Development:

  • The NXG strain (NOD-Prkdcscid-IL2rgtm1/Rj) was generated through homologous recombination of the IL2rgtm1 mutation using B6N mouse embryonic stem cells.
  • In 2019, Janvier Labs developed the congenic NXG model through speed backcrossing (N=5) onto the NOD background.
  • The IL15 gene was inserted into the murine Il15 loci using CRISPR technology in 2023.

Breeding and Maintenance: Animals are bred to retain both the genetic background and key mutations in their homozygous state. The phenotype of the hIL-15 NXG strain is continually monitored in line with Janvier Labs’ Genetic Policy to ensure stability and consistency.

Main application and research fields

Immunology Immunotherapy Infectious diseases Oncology Transplantation


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