Abnormal gene expression in cloned mice derived from embryonic stem cell and cumulus cell nuclei

Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12889-94. doi: 10.1073/pnas.192433399. Epub 2002 Sep 16.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Northern
  • Cell Nucleus / metabolism*
  • Down-Regulation
  • Embryo, Mammalian / cytology
  • Female
  • Gene Expression
  • Liver / metabolism
  • Male
  • Mice
  • Oligonucleotide Array Sequence Analysis
  • Oocytes / metabolism*
  • Placenta / metabolism
  • RNA / analysis
  • Stem Cells / cytology
  • Up-Regulation

Substances

  • RNA