|Draghia-Akli, Ruxandra - ADVISYS, INC.|
Submitted to: Journal of Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: September 11, 2003
Publication Date: August 1, 2004
Citation: Draghia-Akli, R., Fiorotto, M.L. 2004. A new plasmid-mediated approach to supplement somatotropin production in pigs. Journal of Animal Science. 82(8)[E. Suppl.]:E264-E269. Interpretive Summary: The paper summarizes the work we have accomplished in developing and applying a gene transfer approach, similar to DNA vaccinations, to supplement growth hormone (GH) in pigs. This approach uses the gene for GH-releasing hormone (GHRH) in the form of a plasmid vector which is injected intramuscularly in piglets at 10 days of age. The protein encoded by the gene is secreted into the circulation where it can stimulate the pig to increase its own production of GH. We have shown that the age, muscle, dose of plasmid, and type of electrode used for electroporation can influence the efficacy of the procedure and, that as little as 0.1 mg of DNA, will enhance weight gain and produce leaner animals. When the plasmid was administered to pregnant sows, the offspring were born heavier and had greater postnatal weight gain with an improvement in feed efficiency. There was also a significant reduction in the morbidity and mortality of the offspring, an effect that is of significant economic value to producers independently of the effects on growth efficiency.
Technical Abstract: Tremendous progress has been made in the identification of the stimulatory molecules that regulate growth, the mechanisms of action, and the potential application of these molecules for livestock production. A parallel and significant effort is now focused on the discovery and development of economically feasible gene delivery technologies. Plasmid-mediated GHRH gene transfer has emerged as an excellent candidate for agricultural applications to optimize production and animal welfare. We have engineered a GHRH-expressing plasmid that is efficiently expressed in skeletal muscle following intramuscular injection enhanced by electroporation. The GHRH is synthesized in the injected muscle, from which it is secreted to circulate and stimulate normal pituitary GH production and release. Young pigs directly injected with as little as 0.1 mg of a GHRH-expressing plasmid had greater (P < 0.01) weight gain than controls, and a increase (P < 0.05) in fat-free mass. We also have demonstrated that the offspring of gilts injected intramuscularly at d 85 of gestation with a GHRH-expressing plasmid have optimized growth characteristics due to both improved intrauterine weight gain and enhanced maternal lactation performance. Thus, the piglets from treated gilts were larger at birth and weaning compared to controls and reached market weight earlier (P < 0.001). Additionally, pituitaries collected from this group contained an increased number of somatotrophs and lactotrophs (P < 0.001) at birth and at 100 kg. An additional advantage of administering the GHRH plasmid to the gilt compared with the administration of growth-promoting agents to the individual adult animal is a substantial decrease in offspring morbidity and mortality (P < 0.01), which has always represented a major economic loss for the swine industry.