Lab Anim Res.  2024 Dec;40(4):487-497. 10.1186/s42826-024-00231-5.

Immune deficiency phenotypes of Il2rg, Rag2 or Il2rg/Rag2 double knockout rats; establishment of human leukemia xenograft models

• Kim J
• Lim H
• Kwon E
• Mashimo T
• Kang B

• KMID: 2564223
• DOI: http://doi.org/10.1186/s42826-024-00231-5

Abstract

Background
Genetically immunodeficient mice lacking Il2rg and Rag2 genes have been widely utilized in the field of biomedical research. However, immunodeficient rats, which offer the advantage of larger size, have not been as extensively used to date. Recently, Severe Combined Immunodeficiency (SCID) rats were generated using CRISPR/ Cas9 system, targeting Il2rg and Rag2 in National BioResource Project in Japan. We imported and investigated more detailed phenotypes of wild-type (WT) Il2rg knockout (KO), Rag2 KO and Il2rg/Rag2 KO rats for 20 weeks.
Results
During experiments, Il2rg KO, Rag2 KO and Il2rg/Rag2 KO rats showed decreased white blood cells and sys‑ temic lymphopenia, with reduced CD4+, CD8+ T cells and CD161+ NK cells. Additionally, all KO strains exhibited reduced relative spleen weights, hypoplasia of the germinal center in the white pulp, and atrophy with the disap‑ pearance of the boundary between the cortex and medulla in the thymus, compared to WT rats. Furthermore, we established human acute lymphoblastic leukemia xenograft rat model by intravenously injecting 5.0 × ­10⁶ cells/kg of NALM6 cells into Il2rg/Rag2 KO rats.
Conclusions
These findings indicate that Il2rg KO, Rag2 KO, and Il2rg/Rag2 KO rats exhibited SCID phenotypes, sug‑ gesting their potential application as immunodeficient animal models for tumor xenograft studies.

Keyword

SCID rat; Phenotype; Immunodeficiency; Human leukemia xenograft model