Expression profiling of placentomegaly associated with nuclear transplantation of mouse ES cells

Hiroshi Suemizu, Kazuhiro Aiba, Toshiyuki Yoshikawa, Alexei A. Sharov, Nobuhiro Shimozawa, Norikazu Tamaoki, Minoru S.H. Ko

Research output: Contribution to journalArticlepeer-review

66 Citations (Scopus)


Transplantation of nuclei (NT) from engineered mouse ES cells is a potentially powerful and rapid route to create knockout mice, obviating the need for matings to obtain germ-line chimeras. However, such an application is currently impossible, because NT often results in abnormalities in embryo and placenta. Although the epigenetic instability of several imprinted genes in ES cells and ES-derived NT mice has been demonstrated, it is not clear yet what causes the abnormalities. To gain perspective on the extent and types of changes, we have done gene expression profiling for mouse placentas produced by NT of ES cells and compared them with the expression profiles of placentas produced by NT of one-cell embryos. Based on microarray studies with the NIA 15K mouse cDNA collection, we report five principal aberrant events: (1) inappropriate expression of imprinted genes; (2) altered expression of regulatory genes involved in global gene expression, such as DNA methyltransferase and histone acetyltransferase; (3) increased expression of oncogenes and growth promoting genes; (4) overexpression of genes involved in placental growth, such as Plac1; and (5) identification of many novel genes overexpressed in ES-derived NT mouse placentas, including Pitrm1, a new member of the metalloprotease family. The results indicate that placentomegaly in ES-derived NT mice is associated with large-scale dysregulation of normal gene expression patterns. The study also suggests the presence of two regulatory pathways that may lead to histologically discernable placentomegaly. The discovery of groups of genes with altered expression may provide potential targets for intervention to mimic natural regulation more faithfully in NT mice.

Original languageEnglish
Pages (from-to)36-53
Number of pages18
JournalDevelopmental Biology
Issue number1
Publication statusPublished - 2003
Externally publishedYes


  • ES cell
  • Expression profiling
  • Gene expression
  • NIA mouse 15k cDNA microarray
  • Nuclear transplantation
  • Placentomegaly

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology


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