A nude mutant rat derived from Sprague Dawley-National Institute of Nutrition rat colony with normal thymus: A potential model for noncommunicable diseases.

Abstract

A spontaneous mutant rat with a hairless phenotype and an intact thymus was discovered in a long-standing Sprague Dawley-National Institute of Nutrition (SD/NIN) rat colony at a national animal resource facility. We conducted extensive phenotypic and biochemical analyses on this mutant strain to determine its suitability as a preclinical model for immunocompetent testing in noncommunicable disease research. We subjected the mutant rats to strict and frequent phenotypic and genetic surveillance to accomplish this objective. The animals were assessed for food intake, body weight, blood cell profile, clinical chemistry, adipose tissue deposition, and bone mineral density (BMD) using total electrical body conductance (TOBEC) and dual-energy X-ray absorptiometry (DXA) analysis. 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 indicate that the mutant colony propagated from these unique pups displayed distinct phenotypic features and exhibited differences in feeding behavior, weight gain, and clinical biochemistry. The food conversion rate 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, BMD was only slightly lower (7%-8%) compared to the heterozygous groups. These findings indicate that the spontaneous mutant rat has the potential to serve as an immunopotent and modulatory testing system in pharmacokinetics/pharmacodynamics and toxicology, which can be further explored for therapeutic drug discovery.