Pharmacokinetic Evaluation of Colchicine and Hydrochlorothiazide in Sinclair and Gottingen Miniature Swine

With a larger size test animal, more 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, body weight, and nutritional management to reduce the total body mass in adult Sinclair S-1 MS. A large baseline single nucleotide polymorphism (SNP) bank was established for each breeder of the Sinclair MS colony. The SNPs were then used to calculate genomic estimated breeding values for body weight of the breeding animals. Finally, a computer algorithm manipulates a large dataset of phenotypic and genomic data to determine the optimal mating combinations to result in a reduction in adult body mass. Utilizing these selection criteria, we have observed an 8% decline in body size per year in the Sinclair S-1 MS. Concurrently nutritional management approaches have been applied to reduce the size of the Sinclair miniature swine (SMS), while maintaining normal physiology and health status as part of a SMS downsizing program. The food regimen used for the SMS has not been optimized for growth management and allows full body weight development while maintaining 20-30% body fat, even during the acute growth phase.After 10 years of this genetic selection, the body weight reduction outcome of the 6thgeneration at 6 and 12months of age, is a significant(p<0.001)reduction in body weight in both (32.0%)and(37.8%) respectively. 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 and average daily gain to standardize the Downsized Sinclair S-1 MS over the course of the next several generations.

Brocksmith, D.F.², Bouchard, G.F.^1,2 Pannu, M.¹, Miller, W.M.²

¹Sinclair Research an AltasciencesCompany, Auxvasse, MO
²Sinclair Bio Resources, Auxvasse, MO, USA