Genetics, Vol. 167, 897-905, June 2004, Copyright © 2004
doi:10.1534/genetics.103.025049

Paternal Mitochondrial DNA Transmission During Nonhuman Primate Nuclear Transfer

* Mitochondrial and Reproductive Genetics Group, Division of Medical Sciences, University of Birmingham, Birmingham B15 2TH, United Kingdom
{dagger} Pittsburgh Development Center, Magee-Women's Research Institute, Departments of Obstetrics-Gynecology-Reproductive Sciences and Cell Biology-Physiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213

1 Corresponding author: Pittsburgh Development Center, 300 Halket St., Pittsburgh, PA 15213.
E-mail: gschatten{at}pdc.magee.edu

Offspring produced by nuclear transfer (NT) have identical nuclear DNA (nDNA). However, mitochondrial DNA (mtDNA) inheritance could vary considerably. In sheep, homoplasmy is maintained since mtDNA is transmitted from the oocyte (recipient) only. In contrast, cattle are heteroplasmic, harboring a predominance of recipient mtDNA along with varying levels of donor mtDNA. We show that the two nonhuman primate Macaca mulatta offspring born by NT have mtDNA from three sources: (1) maternal mtDNA from the recipient egg, (2) maternal mtDNA from the egg contributing to the donor blastomere, and (3) paternal mtDNA from the sperm that fertilized the egg from which the donor blastomere was isolated. The introduction of foreign mtDNA into reconstructed recipient eggs has also been demonstrated in mice through pronuclear injection and in humans through cytoplasmic transfer. The mitochondrial triplasmy following M. mulatta NT reported here forces concerns regarding the parental origins of mtDNA in clinically reconstructed eggs. In addition, mtDNA heteroplasmy might result in the embryonic stem cell lines generated for experimental and therapeutic purposes ("therapeutic cloning").




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