Engineering of Systematic Elimination of a Targeted Chromosome in Human Cells

Hiroshi Sato, Hiroki Kato, Haruyoshi Yamaza, Keiji Masuda, Huong Thi Nguyen Nguyen, Thanh Thi Mai Pham, Xu Han, Yuta Hirofuji, Kazuaki Nonaka

研究成果: ジャーナルへの寄稿記事

抄録

Embryonic trisomy leads to abortion or congenital genetic disorders in humans. The most common autosomal chromosome abnormalities are trisomy of chromosomes 13, 18, and 21. Although alteration of gene dosage is thought to contribute to disorders caused by extra copies of chromosomes, genes associated with specific disease phenotypes remain unclear. To generate a normal cell from a trisomic cell as a means of etiological analysis or candidate therapy for trisomy syndromes, we developed a system to eliminate a targeted chromosome from human cells. Chromosome 21 was targeted by integration of a DNA cassette in HeLa cells that harbored three copies of chromosome 21. The DNA cassette included two inverted loxP sites and a herpes simplex virus thymidine kinase (HSV-tk) gene. This system causes missegregation of chromosome 21 after expression of Cre recombinase and subsequently enables the selection of cells lacking the chromosome by culturing in a medium that includes ganciclovir (GCV). Cells harboring only two copies of chromosome 21 were efficiently induced by transfection of a Cre expression vector, indicating that this approach is useful for eliminating a targeted chromosome.

元の言語英語
記事番号6037159
ジャーナルBioMed Research International
2017
DOI
出版物ステータス出版済み - 1 1 2017

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Chromosomes, Human, Pair 21
Human Chromosomes
Chromosomes
Cells
Trisomy
Chromosomes, Human, Pair 18
Chromosomes, Human, Pair 13
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Inborn Genetic Diseases
Ganciclovir
Gene Dosage
Thymidine Kinase
Genes
DNA
Simplexvirus
HeLa Cells
Chromosome Aberrations
Transfection
Phenotype
Viruses

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

これを引用

Engineering of Systematic Elimination of a Targeted Chromosome in Human Cells. / Sato, Hiroshi; Kato, Hiroki; Yamaza, Haruyoshi; Masuda, Keiji; Nguyen, Huong Thi Nguyen; Pham, Thanh Thi Mai; Han, Xu; Hirofuji, Yuta; Nonaka, Kazuaki.

:: BioMed Research International, 巻 2017, 6037159, 01.01.2017.

研究成果: ジャーナルへの寄稿記事

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AU - Nguyen, Huong Thi Nguyen

AU - Pham, Thanh Thi Mai

AU - Han, Xu

AU - Hirofuji, Yuta

AU - Nonaka, Kazuaki

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