Rag2 is essential for T and B cell development, while Il2rg is crucial for various immune cell functions. B-SDG rats, with both Rag2 and Il2rg genes knocked out, exhibit severe immunodeficiency. Immune profiling showed the absence of B and T cells, and reduced spleen and thymus weights. Successful xenograft implantation and efficacy studies with various tumors in B-SDG rats demonstrate their utility as a preclinical model for drug candidate evaluation.