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Proc Natl Acad Sci U S A. 2018 Jan 23;115(4):708-713. doi: 10.1073/pnas.1715940115. Epub 2018 Jan 8.

Modeling lethal X-linked genetic disorders in pigs with ensured fertility.

Author information

1
Meiji University International Institute for Bio-Resource Research, Kawasaki 214-8571, Japan.
2
Laboratory of Developmental Engineering, Meiji University, Kawasaki 214-8571, Japan.
3
National Center for Child Health and Development, Tokyo 157-0074, Japan.
4
Institute of Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig-Maximilian University Munich, D-81377 Munich, Germany.
5
Division of Regenerative Medicine, Center for Molecular Medicine, Jichi Medical University, Tochigi 329-0498, Japan.
6
Division of Stem Cell Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
7
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305.
8
Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305.
9
Meiji University International Institute for Bio-Resource Research, Kawasaki 214-8571, Japan; hnagas@meiji.ac.jp.

Abstract

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.

KEYWORDS:

blastocyst complementation; chimera; disease model pig; gene knockout; somatic cell cloning

PMID:
29311328
PMCID:
PMC5789933
DOI:
10.1073/pnas.1715940115
[Indexed for MEDLINE]
Free PMC Article

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