Modeling disease in swine by transplantation of gene targeted germ cells.

DESCRIPTION (provided by applicant): Swine models of human disease will become increasingly important for the development of relevant, preclinical therapeutics. However, the creation of swine congenital disease models is plagued by inefficiencies related to animal development and reproduction. The contemporary method for development relies on somatic cell nuclear transfer (SCNT) of genetically modified primary cells. While effective for the development of founders, cloning is not suitable for the creation of enough animals to meet the biomedical research market, requiring instead a production breeding program. The phenotype of affected animals may be inconsistent with long-term viability and/or sexual reproduction, so disease alleles need to be propagated asheterozygotes. However, a breeding program based on heterozygotes is slow and results in the only 1/4 of the production being affected offspring, dramatically increasing the cost of swine model production. As a solution we propose to develop and pro