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Session IV – Chromosome Engineering

The use of chromosome-based vectors for animal transgenesis

Gene Therapy volume 9, pages 708–712 (2002)Cite this article

Abstract

This article summarizes our efforts to use chromosome-based vectors for animal transgenesis, which may have a benefit for overcoming the size constraints of cloned transgenes in conventional techniques. Since the initial trial for introducing naturally occurring human chromosome fragments (hCFs) with large and complex immunogulobulin (Ig) loci into mice we have obtained several lines of trans-chromosomic (Tc) mice with transmittable hCFs. As expected the normal tissue-specific expression of introduced human genes was reproduced in them by inclusion of essential remote regulatory elements. Recent development of ‘chromosome cloning’ technique that enable construction of human artificial chromosomes (HACs) containing a defined chromosomal region should prevent the introduction of additional genes other than genes of interest and thus enhance the utility of chromosome vector system. Using this technique a panel of HACs harboring inserts ranging in size from 1.5 to 10 Mb from three human chromosomes (hChr2, 7, 22) has been constructed. Tc animals containing the HACs may be valuable not only as a powerful tool for functional genomics but also as an in vivo model to study therapeutic gene delivery by HACs.

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Acknowledgements

We wish to thank S Tanaka, S Igami, T Ishihara, M Shionoya for excellent technical assistance. We also thank K Hanaoka and M Hayasaka for technical advice and valuable discussions.

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Authors and Affiliations

  1. Pharmaceutical Research Laboratory, Kirin Brewery Co Ltd, Gunma, Japan

    Y Kuroiwa, H Yoshida, T Ohshima, A Ohguma, I Ishida & K Tomizuka

  2. Department of Molecular and Cell Genetics, School of Life Sciences, Faculty of Medicine, Tottori University, Tottori, Japan

    T Shinohara, Y Kazuki & M Oshimura

Authors
  1. Y Kuroiwa
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  2. H Yoshida
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  3. T Ohshima
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  4. T Shinohara
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  5. A Ohguma
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  6. Y Kazuki
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  7. M Oshimura
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  8. I Ishida
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  9. K Tomizuka
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Kuroiwa, Y., Yoshida, H., Ohshima, T. et al. The use of chromosome-based vectors for animal transgenesis. Gene Ther 9, 708–712 (2002). https://doi.org/10.1038/sj.gt.3301754

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