Rescuing valuable genomes by animal cloning: a case for natural disease resistance in cattle

Tissue banking and animal cloning represent a powerful tool for conserving and regenerating valuable animal genomes. Here we report an example involving cattle and the rescue of a genome affording natural disease resistance. During the course of a 2-decade study involving the phenotypic and genotypic analysis for the functional and genetic basis of natural disease resistance against bovine brucellosis, a foundation sire was identified and confirmed to be genetically resistant to Brucella abortus. This unique animal was utilized extensively in numerous animal breeding studies to further characterize the genetic basis for natural disease resistance. The bull died in 1996 of natural causes, and no semen was available for AI, resulting in the loss of this valuable genome. Fibroblast cell lines had been established in 1985, cryopreserved, and stored in liquid nitrogen for future genetic analysis. Therefore, we decided to utilize these cells for somatic cell nuclear transfer to attempt the production of a cloned bull and salvage this valuable genotype. Embryos were produced by somatic cell nuclear transfer and transferred to 20 recipient cows, 10 of which became pregnant as determined by ultrasound at d 40 of gestation. One calf survived to term. At present, the cloned bull is 4.5 yr old and appears completely normal as determined by physical examination and blood chemistry. Furthermore, in vitro assays performed to date indicate this bull is naturally resistant to B. abortus, Mycobacterium bovis, and Salmonella typhimurium, as was the original genetic donor.