A Nude Mutant Derived from Five Decades-Old Rat Colony with an Immuno-potent Character - A Potential Model for Non-Communicable Diseases.

Abstract

Background: A spontaneous mutant rat with a hairless phenotype and an intact thymus was discovered in a long-standing SD/NIN rat colony at a national animal resource facility. Objective: We conducted extensive phenotypic and biochemical analyses on this mutant strain to determine its suitability as a preclinical model for immunocompetent testing in non-communicable disease research. Methodology: To accomplish this objective, we subjected the mutant rats to strict and frequent phenotypic and genetic surveillance. We assessed their food intake, body weight, blood cell profile, clinical chemistry, adipose tissue deposition, and bone mineral density using TOBEC and DXA analysis. Results: Initially, only two hairless mutant rats, a male and a female, were born from a single dam in the SD/NIN rat strain. However, the results indicates that the mutant colony propagated from these unique pups displayed distinct phenotypic features and exhibited differences in feeding behaviour, weight gain, and clinical biochemistry. The food conversion rate (FCR) was significantly higher in nude females (2.8-fold) while 26% lower in nude males. Both sexes of nude rats had significantly higher triglycerides and lower glucose levels in females. However, glucose levels did not change in male nude rats. Furthermore, nude female and male rats had significantly lower fat (TOBEC) and bone mineral content (DXA). Nonetheless, bone mineral density was only slightly lower (7-8%) compared to the heterozygous groups. Conclusion: These findings indicate that the spontaneous mutant rat has the potential to serve as an immuno-potent and modulatory testing system in PK/PD and toxicology, which can be further explored for therapeutic drug discovery.