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Mitochondrial Gene Replacement in Primate Offspring and Embryonic Stem Cells
Mitochondria are found in all eukaryotic cells and contain their own genome (mtDNA). Unlike the nuclear genome which is derived from both the egg and sperm at fertilization, the mtDNA in the embryo are derived almost exclusively from the egg, i.e. is of maternal origin. Mutations in mtDNA contribute...
Autores principales: | , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2774772/ https://www.ncbi.nlm.nih.gov/pubmed/19710649 http://dx.doi.org/10.1038/nature08368 |
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author | Tachibana, Masahito Sparman, Michelle Sritanaudomchai, Hathaitip Ma, Hong Clepper, Lisa Woodward, Joy Li, Ying Ramsey, Cathy Kolotushkina, Olena Mitalipov, Shoukhrat |
author_facet | Tachibana, Masahito Sparman, Michelle Sritanaudomchai, Hathaitip Ma, Hong Clepper, Lisa Woodward, Joy Li, Ying Ramsey, Cathy Kolotushkina, Olena Mitalipov, Shoukhrat |
author_sort | Tachibana, Masahito |
collection | PubMed |
description | Mitochondria are found in all eukaryotic cells and contain their own genome (mtDNA). Unlike the nuclear genome which is derived from both the egg and sperm at fertilization, the mtDNA in the embryo are derived almost exclusively from the egg, i.e. is of maternal origin. Mutations in mtDNA contribute to a diverse range of still 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 nonhuman primate oocytes 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 while 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. |
format | Text |
id | pubmed-2774772 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
record_format | MEDLINE/PubMed |
spelling | pubmed-27747722010-03-17 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 Nature Article Mitochondria are found in all eukaryotic cells and contain their own genome (mtDNA). Unlike the nuclear genome which is derived from both the egg and sperm at fertilization, the mtDNA in the embryo are derived almost exclusively from the egg, i.e. is of maternal origin. Mutations in mtDNA contribute to a diverse range of still 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 nonhuman primate oocytes 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 while 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. 2009-08-26 2009-09-17 /pmc/articles/PMC2774772/ /pubmed/19710649 http://dx.doi.org/10.1038/nature08368 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article 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 |
title | Mitochondrial Gene Replacement in Primate Offspring and Embryonic Stem Cells |
title_full | Mitochondrial Gene Replacement in Primate Offspring and Embryonic Stem Cells |
title_fullStr | Mitochondrial Gene Replacement in Primate Offspring and Embryonic Stem Cells |
title_full_unstemmed | Mitochondrial Gene Replacement in Primate Offspring and Embryonic Stem Cells |
title_short | Mitochondrial Gene Replacement in Primate Offspring and Embryonic Stem Cells |
title_sort | mitochondrial gene replacement in primate offspring and embryonic stem cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2774772/ https://www.ncbi.nlm.nih.gov/pubmed/19710649 http://dx.doi.org/10.1038/nature08368 |
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