Spontaneous clinical and anatomical pathology findings in SDRG rats

The SDRG rat, characterized by a Sprague-Dawley (SD) genetic background with deletion of <i>Rag1</i> and <i>Il2rg</i> genes, has deficiencies in B, T, and natural killer (NK) cells, making it a valuable model for preclinical applications such as tissue transplantation/humanization and assessment of advanced therapeutic products. Limited data exists on spontaneous background findings in this strain, particularly in aging animals. To address this gap, this study investigated clinical and anatomical pathology findings in 83 SDRG rats (40 males and 43 females), aged 10 to 26 weeks. Analyses included hematology, clinical chemistry, bone marrow smears, blood immunophenotyping, necropsy, and histology. Hematology revealed severely reduced lymphocyte counts, with a mild age-related increase in counts. Compared with SD rats, both sexes of SDRG rats had higher neutrophil, monocyte, and eosinophil counts; increased urea and cholesterol; lower albumin and total protein; and higher age-related glutamate dehydrogenase concentrations. Males had longer prothrombin times, while females showed sporadic age-related increases in alanine aminotransferase, aspartate aminotransferase, and triglycerides. Blood immunophenotyping confirmed the absence of circulating B and T lymphocytes and NK cells, alongside increased monocytes. Salient microscopic findings included lymphoid organ hypoplasia and inflammation in kidneys and lungs, with urinary bacterial infections, contributing to a single mortality. Age-related changes included progressive cardiomyopathy, early chronic progressive nephropathy, and early reproductive senescence in females. These findings underscore the SDRG strain's potential as a model for preclinical evaluations of cell-based products and provide an initial reference into background features of this immunodeficient model that might help interpretations of experimental results.