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Genetically engineered pigs play an indispensable role in the study of rare monogenic diseases. Pigs harboring a gene responsible for a specific disease can be efficiently generated via somatic cell cloning. The generation of somatic cell-cloned pigs from male cells with mutation(s) in an X chromosomal gene is a reliable and straightforward method for reproducing X-linked genetic diseases (XLGDs) in pigs. However, the severe symptoms of XLGDs are often accompanied by impaired growth and reproductive disorders, which hinder the reproduction of these valuable model animals. Here, we generated unique chimeric boars composed of mutant cells harboring a lethal XLGD and normal cells. The chimeric boars exhibited the cured phenotype with fertility while carrying and transmitting the genotype of the XLGD. This unique reproduction system permits routine production of XLGD model pigs through the male-based breeding, thereby opening an avenue for translational research using disease model pigs.

Original publication

DOI

10.1073/pnas.1715940115

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

23/01/2018

Volume

115

Pages

708 - 713

Keywords

blastocyst complementation, chimera, disease model pig, gene knockout, somatic cell cloning, Animals, Animals, Genetically Modified, Breeding, Chimera, Cloning, Organism, Disease Models, Animal, Embryo Culture Techniques, Fertility, Gene Knockout Techniques, Genetic Diseases, X-Linked, Genetic Engineering, Male, Nuclear Transfer Techniques, Reproduction, Swine