Adult mice cloned from migrating primordial germ cells

Yukiko Yamazaki, Eleanor W. Low, Yusuke Marikawa, Kazuhiro Iwahashi, Marisa S. Bartolomei, John R. McCarrey, Ryuzo Yanagimachi

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

We previously reported that the genomes of gonadal germ cells at 11.5-19.5 days postcoitum (dpc) are incompetent to support full-term development of cloned mouse embryos. In this study, we performed nuclear transfer using primordial germ cells (PGCs) from earlier stages at 8.5-10.5 dpc. When PGC nuclei at 8.5, 9.5, and 10.5 dpc were transferred into enucleated oocytes, seven cloned embryos developed into full-term offspring. Of these, five, all derived from 8.5- or 9.5-dpc PGCs, developed into healthy adults with normal fertility. Of the remaining two offspring derived from 10.5-dpc PGCs, one died shortly after birth, and the other showed slight growth retardation but subsequently developed into a fertile adult. We examined allele-specific methylation at the imprinted H19 and Snrpn loci in 9.5- to 11.5-dpc PGCs. Although the beginning of methylation erasure was evident on the H19 paternal allele at 9.5 dpc, most PGCs did not demonstrate significant erasure of paternal allele-specific methylation until 10.5 dpc. Maternal allele-specific methylation was largely erased from Snrpn by 10.5 dpc. By 11.5 dpc, the majority of PGCs showed nearly complete or complete erasure of allele-specific methylation in both H19 and Snrpn. These results demonstrate that at least some genomic imprints remain largely intact in 8.5- to 9.5-dpc PGCs and then undergo erasure at ≈10.5 dpc as the PGCs enter the genital ridges. Thus, migrating PGCs at 8.5-9.5 dpc can be successfully used as donors for nuclear transfer, whereas gonadal PGCs at 11.5 dpc and later are incompetent to support full-term development.

Original languageEnglish (US)
Pages (from-to)11361-11366
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number32
DOIs
StatePublished - Aug 9 2005
Externally publishedYes

Keywords

  • DNA methylation imprinted genes
  • Developmental totipotency
  • Nuclear transfer

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Adult mice cloned from migrating primordial germ cells'. Together they form a unique fingerprint.

Cite this