Genetics. Published Articles Ahead of Print: February 1, 2006, Copyright © 2006
doi:10.1534/genetics.105.055145


A more recent version of this article appeared on April 1, 2006.

REGULAR RESEARCH PAPERS

Aberrant nucleo-cytoplasmic cross-talk results in donor cell mtDNA persistence in cloned embryos

Rhiannon E Lloyd 1, Joon-Hee Lee 2, Ramiro Alberio 2, Emma J Bowles 1, João Ramalho-Santos 3, Keith H Campbell 2 and Justin C St. John 1*

1 The University of Birmingham
2 University of Nottingham
3 University of Coimbra

* To whom correspondence should be addressed. E-mail: j.stjohn.1{at}bham.ac.uk.

Submitted on December 28, 2005
Revised on January 24, 2006
Accepted on 31 January 2006


Abstract

Mitochondrial DNA is an extranuclear genome normally maternally inherited through the oocyte. However, the use of nuclear transfer can result in both donor cell and recipient oocyte mitochondrial DNA persisting through to blastocyst and being transmitted to the offspring. The degree of donor mitochondrial DNA transmission appears to be random and currently no evidence exists to explain this phenomenon. In order to determine whether this is a dilution factor or directly related to the transcriptional status of the donor cell in respect of mitochondrial DNA transcription factors, we have generated sheep nuclear transfer embryos using donor cells: 1) possessing their full mitochondrial DNA complement; 2) those partially depleted; and 3) those depleted but containing residual levels. For each donor type, donor mitochondrial DNA persisted in some blastocysts. It is evident from the donor cells used that nuclear-encoded mitochondrial DNA transcription and replication factors persist even after mitochondrial DNA depletion, as do transcripts for some of the mitochondrial encoded genes. These cells are therefore still programmed to drive mitochondrial DNA replication and transcription. In nuclear transfer derived embryos, we have observed the persistence of these nuclear-encoded mitochondrial DNA transcription and replication factors but not in those embryos generated through in vitro fertilisation. Consequently, nucleo-mitochondrial interaction following nuclear transfer is out of sequence as the onset of mitochondrial replication is a post-implantation event.

Key Words: Nuclear transfer, depletion, heteroplasmy, homoplasmy, mitochondrial DNA




This article has been cited by other articles:


Home page
 Stem CellsHome page
E. J. Bowles, R. T. Tecirlioglu, A. J. French, M. K. Holland, and J. C. St. John
Mitochondrial DNA Transmission and Transcription After Somatic Cell Fusion to One or More Cytoplasts
Stem Cells, March 1, 2008; 26(3): 775 - 782.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
J. M. Facucho-Oliveira, J. Alderson, E. C. Spikings, S. Egginton, and J. C. St. John
Mitochondrial DNA replication during differentiation of murine embryonic stem cells
J. Cell Sci., November 15, 2007; 120(22): 4025 - 4034.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
E. J. Bowles, J.-H. Lee, R. Alberio, R. E. I. Lloyd, D. Stekel, K. H. S. Campbell, and J. C. St. John
Contrasting Effects of in Vitro Fertilization and Nuclear Transfer on the Expression of mtDNA Replication Factors
Genetics, July 1, 2007; 176(3): 1511 - 1526.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
A. Amaral, J. Ramalho-Santos, and J. C. St John
The expression of polymerase gamma and mitochondrial transcription factor A and the regulation of mitochondrial DNA content in mature human sperm
Hum. Reprod., June 1, 2007; 22(6): 1585 - 1596.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
E. C. Spikings, J. Alderson, and J. C. St. John
Regulated Mitochondrial DNA Replication During Oocyte Maturation Is Essential for Successful Porcine Embryonic Development
Biol Reprod, February 1, 2007; 76(2): 327 - 335.
[Abstract] [Full Text] [PDF]