Abnormal gene expression in cloned mice derived from embryonic stem cell and cumulus cell nuclei.
To assess the extent of abnormal gene expression in clones, we assessed global gene expression by microarray analysis on RNA from the placentas and livers of neonatal cloned mice derived by nuclear transfer (NT) from both cultured embryonic stem cells and freshly isolated cumulus cells. Direct comparison of gene expression profiles of more than 10,000 genes showed that for both donor cell types approximately 4% of the expressed genes in the NT placentas differed dramatically in expression levels from those in controls and that the majority of abnormally expressed genes were common to both types of clones. Importantly, however, the expression of a smaller set of genes differed between the embryonic stem cell- and cumulus cell-derived clones. The livers of the cloned mice also showed abnormal gene expression, although to a lesser extent, and with a different set of affected genes, than seen in the placentas. Our results demonstrate frequent abnormal gene expression in clones, in which most expression abnormalities appear common to the NT procedure whereas others appear to reflect the particular donor nucleus.
Humpherys
David
D
Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA.
Eggan
Kevin
K
Akutsu
Hidenori
H
Friedman
Adam
A
Hochedlinger
Konrad
K
Yanagimachi
Ryuzo
R
Lander
Eric S
ES
Golub
Todd R
TR
Jaenisch
Rudolf
R
D000818:Animals; D015152:Blotting, Northern; D002467:Cell Nucleus / Q000378:metabolism*; D015536:Down-Regulation; D004622:Embryo, Mammalian / Q000166:cytology; D005260:Female; D015870:Gene Expression; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D009865:Oocytes / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism; D012313:RNA / Q000032:analysis; D013234:Stem Cells / Q000166:cytology; D015854:Up-Regulation
D012313:RNA