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. 2001 May;158(1):351–356. doi: 10.1093/genetics/158.1.351

Complete replacement of the mitochondrial genotype in a Bos indicus calf reconstructed by nuclear transfer to a Bos taurus oocyte.

F V Meirelles 1, V Bordignon 1, Y Watanabe 1, M Watanabe 1, A Dayan 1, R B Lôbo 1, J M Garcia 1, L C Smith 1
PMCID: PMC1461657  PMID: 11333243

Abstract

Due to the exclusively maternal inheritance of mitochondria, mitochondrial genotypes can be coupled to a particular nuclear genotype by continuous mating of founder females and their female offspring to males of the desired nuclear genotype. However, backcrossing is a gradual procedure that, apart from being lengthy, cannot ascertain that genetic and epigenetic changes will modify the original nuclear genotype. Animal cloning by nuclear transfer using host ooplasm carrying polymorphic mitochondrial genomes allows, among other biotechnology applications, the coupling of nuclear and mitochondrial genotypes of diverse origin within a single generation. Previous attempts to use Bos taurus oocytes as hosts to transfer nuclei from unrelated species led to the development to the blastocyst stage but none supported gestation to term. Our aim in this study was to determine whether B. taurus oocytes support development of nuclei from the closely related B. indicus cattle and to examine the fate of their mitochondrial genotypes throughout development. We show that indicus:taurus reconstructed oocytes develop to the blastocyst stage and produce live offspring after transfer to surrogate cows. We also demonstrate that, in reconstructed embryos, donor cell-derived mitochondria undergo a stringent genetic drift during early development leading, in most cases, to a reduction or complete elimination of B. indicus mtDNA. These results demonstrate that cross-subspecies animal cloning is a viable approach both for matching diverse nuclear and cytoplasmic genes to create novel breeds of cattle and for rescuing closely related endangered cattle.

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Selected References

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  1. Anderson S., de Bruijn M. H., Coulson A. R., Eperon I. C., Sanger F., Young I. G. Complete sequence of bovine mitochondrial DNA. Conserved features of the mammalian mitochondrial genome. J Mol Biol. 1982 Apr 25;156(4):683–717. doi: 10.1016/0022-2836(82)90137-1. [DOI] [PubMed] [Google Scholar]
  2. Barrientos A., Kenyon L., Moraes C. T. Human xenomitochondrial cybrids. Cellular models of mitochondrial complex I deficiency. J Biol Chem. 1998 Jun 5;273(23):14210–14217. doi: 10.1074/jbc.273.23.14210. [DOI] [PubMed] [Google Scholar]
  3. Bordignon V., Smith L. C. Telophase enucleation: an improved method to prepare recipient cytoplasts for use in bovine nuclear transfer. Mol Reprod Dev. 1998 Jan;49(1):29–36. doi: 10.1002/(SICI)1098-2795(199801)49:1<29::AID-MRD4>3.0.CO;2-Q. [DOI] [PubMed] [Google Scholar]
  4. Brown W. M., George M., Jr, Wilson A. C. Rapid evolution of animal mitochondrial DNA. Proc Natl Acad Sci U S A. 1979 Apr;76(4):1967–1971. doi: 10.1073/pnas.76.4.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dominko T., Mitalipova M., Haley B., Beyhan Z., Memili E., McKusick B., First N. L. Bovine oocyte cytoplasm supports development of embryos produced by nuclear transfer of somatic cell nuclei from various mammalian species. Biol Reprod. 1999 Jun;60(6):1496–1502. doi: 10.1095/biolreprod60.6.1496. [DOI] [PubMed] [Google Scholar]
  6. Evans M. J., Gurer C., Loike J. D., Wilmut I., Schnieke A. E., Schon E. A. Mitochondrial DNA genotypes in nuclear transfer-derived cloned sheep. Nat Genet. 1999 Sep;23(1):90–93. doi: 10.1038/12696. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gyllensten U., Wharton D., Wilson A. C. Maternal inheritance of mitochondrial DNA during backcrossing of two species of mice. J Hered. 1985 Sep-Oct;76(5):321–324. doi: 10.1093/oxfordjournals.jhered.a110103. [DOI] [PubMed] [Google Scholar]
  8. Hiendleder S., Schmutz S. M., Erhardt G., Green R. D., Plante Y. Transmitochondrial differences and varying levels of heteroplasmy in nuclear transfer cloned cattle. Mol Reprod Dev. 1999 Sep;54(1):24–31. doi: 10.1002/(SICI)1098-2795(199909)54:1<24::AID-MRD4>3.0.CO;2-S. [DOI] [PubMed] [Google Scholar]
  9. Irwin M. H., Johnson L. W., Pinkert C. A. Isolation and microinjection of somatic cell-derived mitochondria and germline heteroplasmy in transmitochondrial mice. Transgenic Res. 1999 Apr;8(2):119–123. doi: 10.1023/a:1008925419758. [DOI] [PubMed] [Google Scholar]
  10. Jenuth J. P., Peterson A. C., Fu K., Shoubridge E. A. Random genetic drift in the female germline explains the rapid segregation of mammalian mitochondrial DNA. Nat Genet. 1996 Oct;14(2):146–151. doi: 10.1038/ng1096-146. [DOI] [PubMed] [Google Scholar]
  11. Kenyon L., Moraes C. T. Expanding the functional human mitochondrial DNA database by the establishment of primate xenomitochondrial cybrids. Proc Natl Acad Sci U S A. 1997 Aug 19;94(17):9131–9135. doi: 10.1073/pnas.94.17.9131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Loftus R. T., MacHugh D. E., Bradley D. G., Sharp P. M., Cunningham P. Evidence for two independent domestications of cattle. Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2757–2761. doi: 10.1073/pnas.91.7.2757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Meirelles F. V., Smith L. C. Mitochondrial genotype segregation during preimplantation development in mouse heteroplasmic embryos. Genetics. 1998 Feb;148(2):877–883. doi: 10.1093/genetics/148.2.877. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Meirelles F. V., Smith L. C. Mitochondrial genotype segregation in a mouse heteroplasmic lineage produced by embryonic karyoplast transplantation. Genetics. 1997 Feb;145(2):445–451. doi: 10.1093/genetics/145.2.445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Parrish J. J., Susko-Parrish J. L., Leibfried-Rutledge M. L., Critser E. S., Eyestone W. H., First N. L. Bovine in vitro fertilization with frozen-thawed semen. Theriogenology. 1986 Apr;25(4):591–600. doi: 10.1016/0093-691x(86)90143-3. [DOI] [PubMed] [Google Scholar]
  16. Pikó L., Taylor K. D. Amounts of mitochondrial DNA and abundance of some mitochondrial gene transcripts in early mouse embryos. Dev Biol. 1987 Oct;123(2):364–374. doi: 10.1016/0012-1606(87)90395-2. [DOI] [PubMed] [Google Scholar]
  17. Powell R., Barnes F. L. The kinetics of oocyte activation and polar body formation in bovine embryo clones. Mol Reprod Dev. 1992 Sep;33(1):53–58. doi: 10.1002/mrd.1080330108. [DOI] [PubMed] [Google Scholar]
  18. Solter D., Aronson J., Gilbert S. F., McGrath J. Nuclear transfer in mouse embryos: activation of the embryonic genome. Cold Spring Harb Symp Quant Biol. 1985;50:45–50. doi: 10.1101/sqb.1985.050.01.008. [DOI] [PubMed] [Google Scholar]
  19. Steinborn R., Schinogl P., Zakhartchenko V., Achmann R., Schernthaner W., Stojkovic M., Wolf E., Müller M., Brem G. Mitochondrial DNA heteroplasmy in cloned cattle produced by fetal and adult cell cloning. Nat Genet. 2000 Jul;25(3):255–257. doi: 10.1038/77000. [DOI] [PubMed] [Google Scholar]
  20. Steinborn R., Zakhartchenko V., Wolf E., Müller M., Brem G. Non-balanced mix of mitochondrial DNA in cloned cattle produced by cytoplast-blastomere fusion. FEBS Lett. 1998 Apr 24;426(3):357–361. doi: 10.1016/s0014-5793(98)00351-2. [DOI] [PubMed] [Google Scholar]
  21. Takeda K., Takahashi S., Onishi A., Goto Y., Miyazawa A., Imai H. Dominant distribution of mitochondrial DNA from recipient oocytes in bovine embryos and offspring after nuclear transfer. J Reprod Fertil. 1999 Jul;116(2):253–259. doi: 10.1530/jrf.0.1160253. [DOI] [PubMed] [Google Scholar]
  22. Takeda K., Takahashi S., Onishi A., Hanada H., Imai H. Replicative advantage and tissue-specific segregation of RR mitochondrial DNA between C57BL/6 and RR heteroplasmic mice. Genetics. 2000 Jun;155(2):777–783. doi: 10.1093/genetics/155.2.777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Wilmut I., Schnieke A. E., McWhir J., Kind A. J., Campbell K. H. Viable offspring derived from fetal and adult mammalian cells. Nature. 1997 Feb 27;385(6619):810–813. doi: 10.1038/385810a0. [DOI] [PubMed] [Google Scholar]

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