A research group at Meiji University and Tottori University has succeeded in producing pigs into which human artificial chromosomes have been introduced for the first time in the world by utilizing artificial chromosome introduction technology and somatic cell cloning technology.
Due to their anatomical and physiological similarity to humans, pigs are highly useful in many medical researches, such as faithfully reproducing human pathologies that cannot be reproduced in mice.In particular, genetically modified pigs are a very important research resource, and many transgenic pigs, including disease model pigs, have been created.However, it is still difficult to produce pigs into which a very large (several millions of base pairs) gene has been introduced, and this is a major issue.
In this study, we focused on human artificial chromosomes, which could be an epoch-making carrier of large genes and multiple genes.A human artificial chromosome (DYS-HAC) loaded with a very large full-length human dystrophin gene was prepared and introduced into porcine fibroblasts by chromosome transfer technology (micronuclear cell fusion method).Furthermore, by somatic cell cloning technology, we succeeded in producing a pig with DYS-HAC introduced throughout the body by producing clone cells using DYS-HAC-introduced cells as nuclear donors.
By applying this to pigs that develop Duchenne muscular dystrophy (DMD), a genetic disease, we investigated the therapeutic effect of DMD with human artificial chromosomes.About 1% of pigs that develop DMD usually die within one month after birth, but all four DYS-HAC pigs produced in this study survived at one month of age.Expression of human dystrophin derived from DYS-HAC was observed in muscle, and significant improvement in pathological conditions such as recovery of hindlimb motor function was also observed.
This study was the first in the world to succeed in producing pigs into which artificial chromosomes were introduced, suggesting the usefulness of artificial chromosomes in the treatment of hereditary diseases.In addition, the possibility of creating genetically modified pigs by introducing large genes has great potential, and the development of treatment methods using new human disease model pigs, regenerative medicine, xenotransplantation, etc. It is expected that medical research will accelerate.
