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BOR - Papers in Press, published online ahead of print August 24, 2005.
Biol Reprod 2005, 10.1095/biolreprod.105.044958
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BIOLOGY OF REPRODUCTION 73, 1302–1311 (2005)
DOI: 10.1095/biolreprod.105.044958
© 2005 by the Society for the Study of Reproduction, Inc.

Research Article

Variation in Gene Expression and Aberrantly Regulated Chromosome Regions in Cloned Mice1

Takashi Kohda 34 , Kimiko Inoue 45 , Narumi Ogonuki 5, Hiromi Miki 5, Mie Naruse 3, Tomoko Kaneko-Ishino 46 , Atsuo Ogura 45 , and Fumitoshi Ishino 2 34 

Department of Epigenetics,3 Medical Research Institute, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo 101-0062, Japan CREST,4 Japan Science and Technology Agency (JST), Kawaguchi, Saitama 332-0011, Japan BioResource Center,5 RIKEN, Tsukuba, Ibaraki 305-0074, Japan School of Health Sciences,6 Tokai University, Bohseidai, Isehara, Kanagawa 259-1193, Japan

ABSTRACT

DNA microarray analysis was used to determine the precise genome-wide gene expression profiles of somatic cloned mice derived from Sertoli and cumulus cells. It demonstrated unexpectedly large epigenetic diversity in neonatal cloned mice, despite their normal appearance and genetic identity. In three neonatal tissues of the cloned mice, the expression of 9–40% of the genes examined was more than two times higher or lower in donor cell-dependent or -independent manners compared with normal controls. Relatively few (0.4–4%) of the genes exhibited up- or downregulation in the same manner in both types of clone. A cluster analysis of the variation in gene expression led to the identification of several chromosome regions in which gene expression was aberrantly controlled in the somatic clones. These results provide a more complete understanding of how somatic clones differ from each other and from normal individuals produced by sexual reproduction and indicate the significant difficulties that face the application of somatic cloning in regenerative medicine.

cumulus cells, developmental biology, gene regulation, Sertoli cells

FOOTNOTES

1 Supported by grants from CREST, the research program of the Japan Science and Technology Agency (JST), the Uehara Memorial Science Foundation, the Ministries of Health, Labour, and Welfare for Child Health and Development (14-C) and Education, Culture, Sports, Science and Technology of Japan.

2 Correspondence: Fumitoshi Ishino, Department of Epigenetics, Medical Research Institute, Tokyo Medical and Dental University, 2–3–10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062, Japan. FAX: 81 3 5280 8073; fishino.epgn{at}mri.tmd.ac.jp






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Copyright © 2005 by the Society for the Study of Reproduction.