Variation in gene expression and aberrantly regulated chromosome regions in cloned mice.
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.
Kohda
Takashi
T
Department of Epigenetics, Medical Research Institute, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo 101-0062, Japan.
Inoue
Kimiko
K
Ogonuki
Narumi
N
Miki
Hiromi
H
Naruse
Mie
M
Kaneko-Ishino
Tomoko
T
Ogura
Atsuo
A
Ishino
Fumitoshi
F
D000818:Animals; D002875:Chromosomes; D019976:Cloning, Organism; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007668:Kidney / Q000502:physiology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D020411:Oligonucleotide Array Sequence Analysis; D012708:Sertoli Cells / Q000502:physiology