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Cancer and Metastasis Reviews

, Volume 37, Issue 4, pp 633–642 | Cite as

Mitochondrial polymorphisms contribute to aging phenotypes in MNX mouse models

  • Carolyn J. Vivian
  • Travis M. Hagedorn
  • Roy A. Jensen
  • Amanda E. Brinker
  • Danny R. WelchEmail author
Article
First Online:

Abstract

Many inbred strains of mice develop spontaneous tumors as they age. Recent awareness of the impacts of mitochondrial DNA (mtDNA) on cancer and aging has inspired developing a mitochondrial-nuclear exchange (MNX) mouse model in which nuclear DNA is paired with mitochondrial genomes from other strains of mouse. MNX mice exhibit mtDNA influences on tumorigenicity and metastasis upon mating with transgenic mice. However, we also wanted to investigate spontaneous tumor phenotypes as MNX mice age. Utilizing FVB/NJ, C57BL/6J, C3H/HeN, and BALB/cJ wild-type inbred strains, previously documented phenotypes were observed as expected in MNX mice with the same nuclear background. However, aging nuclear matched MNX mice exhibited decreased occurrence of mammary tumors in C3H/HeN mice containing C57BL/6J mitochondria compared to wild-type C3H/HeN mice. Although aging tumor phenotypes appear to be driven by nuclear genes, evidence suggesting that some differences are modified by the mitochondrial genome is presented.

Keywords

Cancer Mitochondria Mouse Aging 
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Notes

Acknowledgements

We want to thank members of the Welch lab for their helpful comments and suggestions. We also thank the Transgenic and Gene-Targeting Institutional Facility at University of Kansas Cancer Center.

Funding information

These studies were funded primarily by Susan G. Komen for the Cure (SAC110037) and the National Foundation for Cancer Research with additional funding from the National Cancer Institute P30-CA168524 (RAJ; DRW).

Compliance with ethical standards

Conflict of interest

D.R. Welch is a co-holder of a patent on the MNX mice. The other authors declare no conflicts of interest.

Supplementary material

10555_2018_9773_Fig5_ESM.png (1.6 mb)
Figure S1

HC MNX mice have a lower incidence of HCC. A-F. Hematoxylin and eosin stained sections of normal liver. A-D. livers obtained from female mice. E-F. livers obtained from male mice. Unlike HH mice which develop hepatomas in 85% of male and female mice. (PNG 1630 kb)

10555_2018_9773_MOESM1_ESM.tif (3.8 mb)
High resolution image (TIF 3884 kb)

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Carolyn J. Vivian
    • 1
  • Travis M. Hagedorn
    • 2
  • Roy A. Jensen
    • 1
    • 3
    • 4
  • Amanda E. Brinker
    • 1
    • 4
  • Danny R. Welch
    • 1
    • 4
    Email author
  1. 1.Department of Cancer BiologyUniversity of Kansas Medical CenterKansas CityUSA
  2. 2.Laboratory Animal ResourcesUniversity of Kansas Medical CenterKansas CityUSA
  3. 3.Department of Pathology and Laboratory MedicineUniversity of Kansas Medical CenterKansas CityUSA
  4. 4.The University of Kansas Cancer CenterKansas CityUSA

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