Cited by 73Animal Genetics and ReproductionRedox biology and oxidative stressGenetics, Aging, and Longevity in Model Organisms

Strain-dependent high-level expression of a transgene for manganese superoxide dismutase is associated with growth retardation and decreased fertility

Raineri, Ines, Carlson, Elaine J, Gacayan, Rhodora, Carra, Scott, Oberley, Terry D, Huang, Ting-Ting, Epstein, Charles J·2001·Free Radical Biology and Medicine

Abstract

Manganese superoxide dismutase (MnSOD) is essential in protecting mitochondria against the damaging effects of superoxide radicals (O(2)(*-)), and increased expression of MnSOD protects cells and transgenic animals from various forms of oxidative stress. In addition, increased levels of MnSOD have been shown to slow down cell growth and induce differentiation. To study the effects of high MnSOD levels in vivo, we generated a series of transgenic mice using a mouse genomic sequence under control of the endogenous promoter. Four transgenic lines produced by pronuclear DNA injection exhibited up to 2-fold elevated MnSOD levels in brain and heart. However, using an embryonic stem cell approach, a line having 10-fold elevated MnSOD levels in the brain and 6- to 7-fold elevated levels in the heart and kidney was generated. Surprisingly, the genetic background of this transgenic line influenced the expression level of the transgene, with DBA/2 (D2) and C57BL/6 (B6) mice exhibiting low- and high-level transgene expression, respectively. This difference was the result of an increased transcription rate of the transgene. High-level MnSOD expression in B6 animals was associated with small size, male infertility, and decreased female fertility. These features are absent on the D2 background and indicate that high levels of MnSOD activity may interfere with normal growth and fertility.

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Crossref · 10.1016/s0891-5849(01)00686-4

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Authors
Raineri, I., Carlson, E. J., Gacayan, R., Carra, S., Oberley, T. D., Huang, T.-T., & Epstein, C. J.
Affiliations
  • University of California, San Francisco (US)
  • University of Wisconsin–Madison (US)
Venue
Free Radical Biology and Medicine
Publisher
Elsevier BV
Published
2001-10
Volume
31
Issue
8
Pages
1018-1030
ISSN
0891-5849 (ISSN-L)
OpenAlex
W2024253991
Cited by
73
References
42
Citations by year
2023: 2 · 2022: 1 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 3 · 2016: 1 · 2015: 2 · 2014: 5 · 2013: 4 · 2012: 6
FWCI
1.09
Type
journal article
Language
en
Open access
closed
Locations
  • Free Radical Biology and Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute on Aging (AG16998, R01AG016998)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Animal Genetics and Reproduction
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Keywords
manganese superoxide dismutase, transgenic mice, growth retardation, male infertility, female fertility, oxidative stress, mitochondrial superoxide, brain, heart, kidney
MeSH terms
Animals, Bone Marrow Cells, Brain, Catalase, Female, Fetal Growth Retardation, Fibroblasts, Glutathione Reductase, Infertility, Leydig Cells, Male, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Transgenic, Myocardium, Species Specificity, Superoxide Dismutase, Transcription, Genetic, Up-Regulation, Zygote Intrafallopian Transfer, Transgenes, Mice

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