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The Absence of Mitochondrial Thioredoxin 2 Causes Massive Apoptosis, Exencephaly, and Early Embryonic Lethality in Homozygous Mice
Open accessAbstract
Thioredoxin 2 (Trx-2) is a small redox protein containing the thioredoxin active site Trp-Cys-Gly-Pro-Cys that is localized to the mitochondria by a mitochondrial leader sequence and encoded by a nuclear gene (Trx-2). Trx-2 plays an important role in cell viability and the regulation of apoptosis in vitro. To investigate the role of Trx-2 in mouse development, we studied the phenotype of mice that have the Trx-2 gene silenced by mutational insertion. Homozygous mutant embryos do not survive to birth and die after implantation at Theiler stage 15/16. The homozygous mutant embryos display an open anterior neural tube and show massively increased apoptosis at 10.5 days postcoitus and are not present by 12.5 days postcoitus. The timing of the embryonic lethality coincides with the maturation of the mitochondria, since they begin oxidative phosphorylation during this stage of embryogenesis. In addition, embryonic fibroblasts cultured from homozygous Trx-2-null embryos were not viable. Heterozygous mice are fertile and have no discernible phenotype visible by external observation, despite having decreased Trx-2 mRNA and protein. These results show that the mitochondrial redox protein Trx-2 is required for normal development of the mouse embryo and for actively respiring cells.
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“Both Trx1 and Trx2 appear to be essential, as complete deficiency of either subtype causes early embryonic lethality in mice (280, 317).”
From Redox regulation of mitochondrial function (2012) · cites this paper as [317]
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Metadata
- Authors
- Nonn, L., Williams, R. R., Erickson, R. P., & Powis, G.
- Affiliations
- University of Arizona (US)
- Corresponding author
- Nonn, Larisa
- Powis, Garth
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2003-02-01
- Volume
- 23
- Issue
- 3
- Pages
- 916-922
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC140716
- OpenAlex
- W2061958603
- Cited by
- 438
- References
- 34
- Citations by year
- 2026: 7 · 2025: 2 · 2024: 9 · 2023: 11 · 2022: 13 · 2021: 14 · 2020: 13 · 2019: 16 · 2018: 17 · 2017: 19 · 2016: 20 · 2015: 28 · 2014: 17 · 2013: 17 · 2012: 18
- FWCI
- 8.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA 23074, R01CA077204, CA77204, P30CA023074)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- thioredoxin 2, mitochondrial thioredoxin, apoptosis, exencephaly, embryonic lethality, neural tube defects, oxidative phosphorylation, mitochondrial maturation, embryonic fibroblasts, heterozygous mice
- MeSH terms
- Animals, Female, Fetal Death, Gestational Age, Heterozygote, Homozygote, Membrane Proteins, Mice, Inbred C57BL, Mitochondria, Neural Tube Defects, Phenotype, Pregnancy, RNA, Messenger, Thioredoxins, Apoptosis, Mice, Knockout, Mice
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