Strain-dependent high-level expression of a transgene for manganese superoxide dismutase is associated with growth retardation and decreased fertility
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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Cardiolipin can be especially damaged by ROS because of its important roles.
“Cardiolipin can be especially damaged by ROS because of these important roles (213, 258, 260, 261).”
From Mitochondrial reactive oxygen species production in excitable cells: Modulators of mitochondrial and cell function (2009) · cites this paper as [258]
Sod2 transgenic mice do not have an increased lifespan compared to wild-type.
“Furthermore, Sod2 transgenic mice do not have an increased lifespan compared to wild-type”
From Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes (2010) · cites this paper as [91]
Depending on the level of transgene expression, Sod2 transgenic mice display growth retardation and decreased fertility.
“depending on the level of transgene expression, these mice display growth retardation and decreased fertility 90, 91.”
From Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes (2010) · cites this paper as [91]
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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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