Skip to main content
PMC home page
Genetics logoLink to Genetics
. 2000 Nov;156(3):1277–1284. doi: 10.1093/genetics/156.3.1277

Selective and continuous elimination of mitochondria microinjected into mouse eggs from spermatids, but not from liver cells, occurs throughout embryogenesis.

H Shitara 1, H Kaneda 1, A Sato 1, K Inoue 1, A Ogura 1, H Yonekawa 1, J I Hayashi 1
PMCID: PMC1461340  PMID: 11063701

Abstract

Exclusion of paternal mitochondria in fertilized mammalian eggs is very stringent and ensures strictly maternal mtDNA inheritance. In this study, to examine whether elimination was specific to sperm mitochondria, we microinjected spermatid or liver mitochondria into mouse embryos. Congenic B6-mt(spr) strain mice, which are different from C57BL/6J (B6) strain mice (Mus musculus domesticus) only in possessing M. spretus mtDNA, were used as mitochondrial donors. B6-mt(spr) mice and a quantitative PCR method enabled selective estimation of the amount of M. spretus mtDNA introduced even in the presence of host M. m. domesticus mtDNA and monitoring subsequent changes of its amount during embryogenesis. Results showed that M. spretus mtDNA in spermatid mitochondria was not eliminated by the blastocyst stage, probably due to the introduction of a larger amount of spermatid mtDNA than of sperm mtDNA into embryos on fertilization. However, spermatid-derived M. spretus mtDNA was eliminated by the time of birth, whereas liver-derived M. spretus mtDNA was still present in most newborn mice, even though its amount introduced was significantly less than that of spermatid mtDNA. These observations suggest that mitochondria from spermatids but not from liver have specific factors that ensure their selective elimination and resultant elimination of mtDNA in them, and that the occurrence of elimination is not limited to early stage embryos, but continues throughout embryogenesis.

Full Text

The Full Text of this article is available as a PDF (284.5 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alcivar A. A., Hake L. E., Millette C. F., Trasler J. M., Hecht N. B. Mitochondrial gene expression in male germ cells of the mouse. Dev Biol. 1989 Oct;135(2):263–271. doi: 10.1016/0012-1606(89)90178-4. [DOI] [PubMed] [Google Scholar]
  2. Ashley M. V., Laipis P. J., Hauswirth W. W. Rapid segregation of heteroplasmic bovine mitochondria. Nucleic Acids Res. 1989 Sep 25;17(18):7325–7331. doi: 10.1093/nar/17.18.7325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bibb M. J., Van Etten R. A., Wright C. T., Walberg M. W., Clayton D. A. Sequence and gene organization of mouse mitochondrial DNA. Cell. 1981 Oct;26(2 Pt 2):167–180. doi: 10.1016/0092-8674(81)90300-7. [DOI] [PubMed] [Google Scholar]
  4. Cummins J. M., Kishikawa H., Mehmet D., Yanagimachi R. Fate of genetically marked mitochondrial DNA from spermatocytes microinjected into mouse zygotes. Zygote. 1999 May;7(2):151–156. doi: 10.1017/s0967199499000519. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Gyllensten U., Wharton D., Josefsson A., Wilson A. C. Paternal inheritance of mitochondrial DNA in mice. Nature. 1991 Jul 18;352(6332):255–257. doi: 10.1038/352255a0. [DOI] [PubMed] [Google Scholar]
  7. Hauswirth W. W., Laipis P. J. Mitochondrial DNA polymorphism in a maternal lineage of Holstein cows. Proc Natl Acad Sci U S A. 1982 Aug;79(15):4686–4690. doi: 10.1073/pnas.79.15.4686. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hayashi J. I., Yonekawa H., Gotoh O., Watanabe J., Tagashira Y. Strictly maternal inheritance of rat mitochondrial DNA. Biochem Biophys Res Commun. 1978 Aug 14;83(3):1032–1038. doi: 10.1016/0006-291x(78)91499-7. [DOI] [PubMed] [Google Scholar]
  9. Hecht N. B., Liem H., Kleene K. C., Distel R. J., Ho S. M. Maternal inheritance of the mouse mitochondrial genome is not mediated by a loss or gross alteration of the paternal mitochondrial DNA or by methylation of the oocyte mitochondrial DNA. Dev Biol. 1984 Apr;102(2):452–461. doi: 10.1016/0012-1606(84)90210-0. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. 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]
  12. Kaneda H., Hayashi J., Takahama S., Taya C., Lindahl K. F., Yonekawa H. Elimination of paternal mitochondrial DNA in intraspecific crosses during early mouse embryogenesis. Proc Natl Acad Sci U S A. 1995 May 9;92(10):4542–4546. doi: 10.1073/pnas.92.10.4542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kimura Y., Yanagimachi R. Mouse oocytes injected with testicular spermatozoa or round spermatids can develop into normal offspring. Development. 1995 Aug;121(8):2397–2405. doi: 10.1242/dev.121.8.2397. [DOI] [PubMed] [Google Scholar]
  14. King M. P., Attardi G. Injection of mitochondria into human cells leads to a rapid replacement of the endogenous mitochondrial DNA. Cell. 1988 Mar 25;52(6):811–819. doi: 10.1016/0092-8674(88)90423-0. [DOI] [PubMed] [Google Scholar]
  15. Kobayashi Y., Momoi M. Y., Tominaga K., Shimoizumi H., Nihei K., Yanagisawa M., Kagawa Y., Ohta S. Respiration-deficient cells are caused by a single point mutation in the mitochondrial tRNA-Leu (UUR) gene in mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS). Am J Hum Genet. 1991 Sep;49(3):590–599. [PMC free article] [PubMed] [Google Scholar]
  16. Larsson N. G., Garman J. D., Oldfors A., Barsh G. S., Clayton D. A. A single mouse gene encodes the mitochondrial transcription factor A and a testis-specific nuclear HMG-box protein. Nat Genet. 1996 Jul;13(3):296–302. doi: 10.1038/ng0796-296. [DOI] [PubMed] [Google Scholar]
  17. Larsson N. G., Garman J. D., Oldfors A., Barsh G. S., Clayton D. A. A single mouse gene encodes the mitochondrial transcription factor A and a testis-specific nuclear HMG-box protein. Nat Genet. 1996 Jul;13(3):296–302. doi: 10.1038/ng0796-296. [DOI] [PubMed] [Google Scholar]
  18. Ogura A., Yanagimachi R. Round spermatid nuclei injected into hamster oocytes from pronuclei and participate in syngamy. Biol Reprod. 1993 Feb;48(2):219–225. doi: 10.1095/biolreprod48.2.219. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Shitara H., Hayashi J. I., Takahama S., Kaneda H., Yonekawa H. Maternal inheritance of mouse mtDNA in interspecific hybrids: segregation of the leaked paternal mtDNA followed by the prevention of subsequent paternal leakage. Genetics. 1998 Feb;148(2):851–857. doi: 10.1093/genetics/148.2.851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sutovsky P., Moreno R. D., Ramalho-Santos J., Dominko T., Simerly C., Schatten G. Ubiquitin tag for sperm mitochondria. Nature. 1999 Nov 25;402(6760):371–372. doi: 10.1038/46466. [DOI] [PubMed] [Google Scholar]
  22. Yamaoka M., Isobe K., Shitara H., Yonekawa H., Miyabayashi S., Hayashi J. I. Complete repopulation of mouse mitochondrial DNA-less cells with rat mitochondrial DNA restores mitochondrial translation but not mitochondrial respiratory function. Genetics. 2000 May;155(1):301–307. doi: 10.1093/genetics/155.1.301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Yonekawa H., Moriwaki K., Gotoh O., Hayashi J. I., Watanabe J., Miyashita N., Petras M. L., Tagashira Y. Evolutionary relationships among five subspecies of Mus musculus based on restriction enzyme cleavage patterns of mitochondrial DNA. Genetics. 1981 Aug;98(4):801–816. doi: 10.1093/genetics/98.4.801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Yonekawa H., Moriwaki K., Gotoh O., Miyashita N., Migita S., Bonhomme F., Hjorth J. P., Petras M. L., Tagashira Y. Origins of laboratory mice deduced from restriction patterns of mitochondrial DNA. Differentiation. 1982;22(3):222–226. doi: 10.1111/j.1432-0436.1982.tb01255.x. [DOI] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES