Miniature swine have many advantages over other species for biomedical research such as their anatomical and physiological similarities to humans. However, one of the disadvantages of the miniature swine for biomedical research such as harmaceutical toxicology can be the size of the animal. With a larger size test animal, a larger amount of test material is required to complete the toxicology study thus increasing cost of the study. The objective of this study was to utilize genomic selection, phenotype and body weight, to reduce the total body mass in adult Sinclair S-1 miniature swine. Initially, a large baseline single nucleotide polymorphism (SNP) bank was established for each breeder of the Sinclair miniature swine colony. The SNPs were then used to calculate genomic estimated breeding values (GEBV) for body weight of the breeding animals.
Finally, we developed a computer algorithm to manipulate a large dataset of phenotypic and genomic data to determine the optimal mating ombinations to result in a reduction in adult body mass. Utilizing this genomic selection criteria, we have observed an 8% decline in body size per year in the Sinclair S-1 miniature swine. After 5 years of this genetic selection, the body weight reduction outcome of the 4thgeneration at 6 months of age, is a significant (p<0.05) reduction in body weight in both males (35.1%) and females (25.1%). Further concurrent studies are being conducted to standardize the clinical pathology, biometric and reproductive variables, as well as validation studies for compound kinetics, dermal irritation, and feeding regimen assessment. We have developed a genomic selection tool based on body mass to down size the Sinclair S-1 miniature swine over the course of the next several generations. As the pig becomes the accepted translational model for biomedical research, we believe that strategically downsizing the Sinclair S-1 miniature swine will allow it be the model of choice for nonclinical toxicology studies.
Brocksmith, D.F., Stricker-Krongrad, A, Bouchard, G.F.