A Novel and Stable Mouse Artificial Chromosome Vector

Takiguchi, Masato; Kazuki, Yasuhiro; Hiramatsu, Kiyoshi; Abe, Satoshi; Iida, Yuichi; Takehara, Shoko; Nishida, Tadashi; Ohbayashi, Tetsuya; Wakayama, Teruhiko; Oshimura, Mitsuo

doi:10.1021/sb3000723

Cited by 64 publications

(101 citation statements)

References 46 publications

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“…Although HACs are stable in human cell lines and some cells and tissues of other species, they have shown variable retention rates in mouse tissues, being especially low in mouse hematopoietic cells with high turnovers [54]. To overcome this problem, MACs were generated by the topdown approach to have the same capacity as HAC vectors with the additional advantage of highly stable maintenance in mouse tissues including hematopoietic cells.…”

Section: Characteristics Of Hacs/macsmentioning

confidence: 99%

“…To overcome this problem, MACs were generated by the topdown approach to have the same capacity as HAC vectors with the additional advantage of highly stable maintenance in mouse tissues including hematopoietic cells. Therefore, MACs are more valuable gene delivery vectors for the production of model mice than HACs [54,55]. Although several groups have developed MACs using different methods, to our knowledge those derived from native mouse chromosomes via the top-down approach are the most stable in mice [56,57].…”

Section: Characteristics Of Hacs/macsmentioning

confidence: 99%

“…In system (a), gene loading with unique sequences in HACs/ MACs via HR in DT40 cells has previously been performed [49,54] (Fig. 3a).…”

Section: Gene-loading Techniques For Hacs/macsmentioning

confidence: 99%

“…3d). For the efficient and convenient production of Tc animals carrying gene(s) of interest, a MAC carrying multi-integration sites (MI-MAC) was also constructed [54]. The MI-MAC has been transferred into mouse ES cells to enable gene(s) of interest to be directly loaded onto it [68].…”

Section: Gene-loading Techniques For Hacs/macsmentioning

confidence: 99%

“…HACs/MACs can deliver entire gene regions with elements for physiological expression, and can maintain defined copy numbers, especially single copies, in model animals [53][54][55]. Therefore, modified SNPs can be more efficiently identified in Tc animals than in conventional genome-edited animals with diploid genomes.…”

Section: Replacement Of Single-nucleotide Polymorphisms In Humanized mentioning

confidence: 99%

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Combinations of chromosome transfer and genome editing for the development of cell/animal models of human disease and humanized animal models

et al. 2017

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Section: Characteristics Of Hacs/macsmentioning

confidence: 99%

Section: Characteristics Of Hacs/macsmentioning

confidence: 99%

“…In system (a), gene loading with unique sequences in HACs/ MACs via HR in DT40 cells has previously been performed [49,54] (Fig. 3a).…”

Section: Gene-loading Techniques For Hacs/macsmentioning

confidence: 99%

Section: Gene-loading Techniques For Hacs/macsmentioning

confidence: 99%

Section: Replacement Of Single-nucleotide Polymorphisms In Humanized mentioning

confidence: 99%

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Combinations of chromosome transfer and genome editing for the development of cell/animal models of human disease and humanized animal models

et al. 2017

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Multiple expression cassette exchange via TP901‐1, R4, and Bxb1 integrase systems on a mouse artificial chromosome

et al. 2017

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The site‐specific excision of a target DNA sequence for genetic knockout or lineage tracing is a powerful tool for investigating biological systems. Currently, site‐specific recombinases (SSRs), such as Cre or Flp recombination target cassettes, have been successfully excised or inverted by a single SSR to regulate transgene expression. However, the use of a single SSR might restrict the complex control of gene expression. This study investigated the potential for expanding the multiple regulation of transgenes using three different integrase systems (TP901‐1, R4, and Bxb1). We designed three excision cassettes that expressed luciferase, where the luciferase expression could be exchanged to a fluorescent protein by site‐specific recombination. Individual cassettes that could be regulated independently by a different integrase were connected in tandem and inserted into a mouse artificial chromosome (MAC) vector in Chinese hamster ovary cells. The transient expression of an integrase caused the targeted luciferase activity to be lost and fluorescence was activated. Additionally, the integrase system enabled the specific excision of targeted DNA sequences without cross‐reaction with the other recombination targets. These results suggest that the combined use of these integrase systems in a defined locus on a MAC vector permits the multiple regulation of transgene expression and might contribute to genomic or cell engineering.

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New Vectors for Gene Delivery: Human and Mouse Artificial Chromosomes

Oshimura

Kazuki

Iida

et al. 2013

Encyclopedia of Life Sciences

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Human artificial chromosomes (HACs) have been generated mainly by either a ‘top‐down approach’ (engineered creation) or a ‘bottom‐up approach’ ( de novo creation). HACs with acceptor sites exhibit several characteristics required by an ideal gene delivery vector, including stable episomal maintenance and capacity to carry large genomic loci plus their regulatory elements, thus allowing the physiological regulation of the introduced gene in a manner similar to that of native chromosomes. Mouse artificial chromosomes (MACs) with acceptor sites were also created from a native mouse chromosome. The microcell‐mediated chromosome transfer (MMCT) technique for manipulating HACs and MACs in donor cells in order to deliver them to recipient cells is required for each approach. This review describes the lessons learned and prospects identified from studies on the construction of HACs and MACs and their ability to drive exogenous gene expression in cultured cells and transgenic animals via MMCT. The recent emergence of stem cell‐based tissue engineering has opened up new avenues for gene and cell therapies, and possible applications for medical use of HACs and MACs are also proposed. Key Concepts: The microcell‐mediated chromosome transfer method can transfer an intact chromosome or chromosome fragment from donor cell to recipient cell. Human artificial chromosome (HAC), which is an episomal vector derived from a native chromosome, has several advantages: it can contain the entire genome sequences of interest including its regulatory regions with long‐term stable maintenance and gene expression in human cells. The de novo HAC (bottom‐up approach) has been developed with alphoid DNA in HT1080 cells under the condition with lower H3K9me3 methylated alphoid DNA concerning cell‐type‐specific barrier for de novo CENP‐A assembly. The tet‐O HAC is a kind of de novo HAC with a conditional centromere which is constructed with alphoid DNA, and tetracycline operator sequence can be inactivated by expression of tet‐repressor fusion protein for loss of the tet‐O HAC. Mouse artificial chromosome (MAC) is a useful tool for the animal transgenesis because it can be maintained stably in mouse cells and transchromosomic mice through germline transmission. HAC/MAC have a loxP site and/or five recombination platforms to insert circular vectors like bacterial artificial chromosome or make a translocation of the targeting region from other chromosomes. HACs could be used for the complete correction of iPS cells from a patient with Duchenne muscular dystrophy. An HAC which contains Klf4, Sox2, Oct4, c‐Myc and siRNA expression against p53 could reprogramme mouse embryonic fibroblast to pluripotent stem cells. Humanised model mice using human artificial chromosomes, which contain the human CYP3A cluster and the human immunoglobulins including whole 700kb or 1Mb genomic region, have been produced. HACs/MACs might be used for a wide variety of purposes including medical and pharmaceutical applications and even for synthetic biology in sophisticated control.

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A Novel and Stable Mouse Artificial Chromosome Vector

Cited by 64 publications

References 46 publications

Combinations of chromosome transfer and genome editing for the development of cell/animal models of human disease and humanized animal models

Combinations of chromosome transfer and genome editing for the development of cell/animal models of human disease and humanized animal models

Multiple expression cassette exchange via TP901‐1, R4, and Bxb1 integrase systems on a mouse artificial chromosome

New Vectors for Gene Delivery: Human and Mouse Artificial Chromosomes

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