"Equine Cloning: Past, Present and Future"

October 5 
Dirk Vanderwall - Animal and Veterinary Science

Abstract: The ability to clone mammals using somatic cell nuclear transfer (e.g., Dolly the sheep) has been recognized as a scientific milestone, because it demonstrated that a fully differentiated somatic cell from the body can be genetically “reprogrammed” back to the undifferentiated state of a one-cell zygote (embryo), which can then initiate and undergo complete embryonic/fetal development resulting in the birth of an animal genetically identical to the original cell donor. Potential uses of equine cloning include: 1) preservation of genetics from individual animals that would otherwise not be able to reproduce such as geldings (castrated males), 2) preservation of genetic material of endangered and/or exotic species such as Przewalski’s horse and 3) because of the companion animal role that horses fill for some individuals, it is likely that some horse owners will have individual animals cloned for emotional fulfillment. Of these, cloning geldings to produce reproductively intact males for breeding purposes will likely be the first direct application of equine cloning. Although some breed associations (e.g., The Jockey Club, American Quarter Horse Association) do not presently allow the registration of cloned animals, for some equine sporting activities (dressage, show-jumping) breed registry status is irrelevant, which eliminates that regulatory impediment to the use of cloning technology.

2003 was a notable year for equine cloning. We reported the birth of three mule foals cloned from a fetal fibroblast cell line (Science 2003;301:1063) and Galli et al. (Nature 2003;424:635) reported the birth of a horse foal cloned from an adult fibroblast cell line. Despite the recent success of equine cloning, like other species, the efficiency of equine cloning is low; less than 3% of cloned embryos produced with our current cloning system result in offspring. Based on experience with other species, the primary problem contributing to the inefficiency of cloning is “cloned offspring syndrome”, which is characterized by a high incidence of embryonic, fetal and/or placental developmental abnormalities that result in extremely high rates of embryonic loss, abortion and stillbirths throughout gestation; and compromised neonatal health after birth. Cloned offspring syndrome has been especially problematic in cattle and sheep where problems are manifested throughout gestation and the neonatal period. The embryonic/fetal and/or placental developmental abnormalities that result in abortion, stillbirth or compromised neonatal health are thought to reflect incomplete or abnormal genetic reprogramming of the donor nucleus, specifically related to critically important imprinted genes. Future work in the area of equine cloning will be directed at understanding the factors that contribute to the current inefficiency of the cloning process, which clearly has relevance to the clinical (future) application of this emerging technology.