Mitochondrial gene replacement in primate offspring and embryonic stem cells

Masahito Tachibana, Michelle Sparman, Hathaitip Sritanaudomchai, Hong Ma, Lisa Clepper, Joy Woodward, Ying Li, Cathy Ramsey, Olena Kolotushkina, Shoukhrat Mitalipov

Research output: Contribution to journalArticle

336 Citations (Scopus)

Abstract

Mitochondria are found in all eukaryotic cells and contain their own genome (mitochondrial DNA or mtDNA). Unlike the nuclear genome, which is derived from both the egg and sperm at fertilization, the mtDNA in the embryo is derived almost exclusively from the egg; that is, it is of maternal origin. Mutations in mtDNA contribute to a diverse range of currently incurable human diseases and disorders. To establish preclinical models for new therapeutic approaches, we demonstrate here that the mitochondrial genome can be efficiently replaced in mature non-human primate oocytes (Macaca mulatta) by spindle-chromosomal complex transfer from one egg to an enucleated, mitochondrial-replete egg. The reconstructed oocytes with the mitochondrial replacement were capable of supporting normal fertilization, embryo development and produced healthy offspring. Genetic analysis confirmed that nuclear DNA in the three infants born so far originated from the spindle donors whereas mtDNA came from the cytoplast donors. No contribution of spindle donor mtDNA was detected in offspring. Spindle replacement is shown here as an efficient protocol replacing the full complement of mitochondria in newly generated embryonic stem cell lines. This approach may offer a reproductive option to prevent mtDNA disease transmission in affected families.

Original languageEnglish (US)
Pages (from-to)367-372
Number of pages6
JournalNature
Volume461
Issue number7262
DOIs
StatePublished - Sep 17 2009

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Mitochondrial Genes
Embryonic Stem Cells
Mitochondrial DNA
Primates
Ovum
Tissue Donors
Fertilization
Oocytes
Mitochondria
Genome
Mitochondrial Genome
Eukaryotic Cells
Macaca mulatta
Embryonic Development
Spermatozoa
Embryonic Structures
Mothers
Cell Line
Mutation
DNA

ASJC Scopus subject areas

  • General

Cite this

Tachibana, M., Sparman, M., Sritanaudomchai, H., Ma, H., Clepper, L., Woodward, J., ... Mitalipov, S. (2009). Mitochondrial gene replacement in primate offspring and embryonic stem cells. Nature, 461(7262), 367-372. https://doi.org/10.1038/nature08368

Mitochondrial gene replacement in primate offspring and embryonic stem cells. / Tachibana, Masahito; Sparman, Michelle; Sritanaudomchai, Hathaitip; Ma, Hong; Clepper, Lisa; Woodward, Joy; Li, Ying; Ramsey, Cathy; Kolotushkina, Olena; Mitalipov, Shoukhrat.

In: Nature, Vol. 461, No. 7262, 17.09.2009, p. 367-372.

Research output: Contribution to journalArticle

Tachibana, M, Sparman, M, Sritanaudomchai, H, Ma, H, Clepper, L, Woodward, J, Li, Y, Ramsey, C, Kolotushkina, O & Mitalipov, S 2009, 'Mitochondrial gene replacement in primate offspring and embryonic stem cells', Nature, vol. 461, no. 7262, pp. 367-372. https://doi.org/10.1038/nature08368
Tachibana M, Sparman M, Sritanaudomchai H, Ma H, Clepper L, Woodward J et al. Mitochondrial gene replacement in primate offspring and embryonic stem cells. Nature. 2009 Sep 17;461(7262):367-372. https://doi.org/10.1038/nature08368
Tachibana, Masahito ; Sparman, Michelle ; Sritanaudomchai, Hathaitip ; Ma, Hong ; Clepper, Lisa ; Woodward, Joy ; Li, Ying ; Ramsey, Cathy ; Kolotushkina, Olena ; Mitalipov, Shoukhrat. / Mitochondrial gene replacement in primate offspring and embryonic stem cells. In: Nature. 2009 ; Vol. 461, No. 7262. pp. 367-372.
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