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Early Embryonic Lethality Caused by Targeted Disruption of the Mouse Thioredoxin Gene
Open accessAbstract
Thioredoxins belong to a widely distributed group of small proteins with strong reducing activities mediated by a consensus redox-active dithiol (Cys-Gly-Pro-Cys). Thioredoxin was first isolated as a hydrogen donor for enzymatic synthesis of deoxyribonucleotides by ribonucleotide reductase in Escherichia coli. Recent studies have revealed a variety of roles that thioredoxin plays in transcription, growth control, and immune function. In this report, we describe the phenotype of mice carrying a targeted disruption of the thioredoxin gene (Txn). Heterozygotes are viable, fertile, and appear normal. In contrast, homozygous mutants die shortly after implantation, and the concepti were resorbed prior to gastrulation. When preimplantation embryos were placed in culture, the inner cell mass cells of the homozygous embryos failed to proliferate. These results indicate that Txn expression is essential for early differentiation and morphogenesis of the mouse embryo.
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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 [280]
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“This suggests that TRX is essential for the early differentiation and morphogenesis of the mouse embryo [19].”
BackgroundSelf-citationRedox-active Protein Thioredoxin Prevents Proinflammatory Cytokine- or Bleomycin-induced Lung Injury
Hoshino, T., Nakamura, H., Okamoto, M., Kato, S., Araya, S., Nomiyama, K., Ōizumi, K., Young, H. A., Aizawa, H., & Yodoi, J. (2003) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200209-982oc · Cited by 151
“These results raise the possibility that loss of TRX function increases sensitivity to bleomycin, although TRX deficiency is lethal (31).”
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Involvement of thio-, peroxi-, and glutaredoxins in cellular redox-dependent processes
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Mandal, P. K., Schneider, M., Kölle, P., Kuhlencordt, P., Förster, H., Beck, H., Bornkamm, G. W., & Conrad, M. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-1509 · Cited by 147
Scalcon, V., Bindoli, A., & Rigobello, M. P. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.03.043 · Cited by 141
Redox Regulation via Glutaredoxin-1 and Protein S -Glutathionylation
Matsui, R., Ferrán, B., Oh, A., Croteau, D., Shao, D., Han, J., Pimentel, D. R., & Bachschmid, M. M. (2019) · Antioxidants and Redox Signaling · doi:10.1089/ars.2019.7963 · Cited by 142
“Unlike the in utero lethality of thioredoxin deletion (119), mice lacking Glrx appear grossly normal.”
Ahsan, M. K., Lekli, I., Ray, D., Yodoi, J., & Das, D. K. (2009) · Antioxidants and Redox Signaling · doi:10.1089/ars.2009.2683 · Cited by 142
“Trx-2 is also an essential protein in mammals, like Trx-1, and together they cause embryonic lethality if they are deficient (114, 138).”
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Self-citationSelenoproteins and the aging brain
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Expression of Glutaredoxin in Human Coronary Arteries
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“5 [130] and knockout of the redox-modulating enzyme, Ref-1 [48,51], is embryonic lethal shortly after implantation [131].”
BackgroundHigh levels of thioredoxin reductase 1 modulate drug-specific cytotoxic efficacy
Eriksson, S. E., Prast‐Nielsen, S., Flaberg, E., Székely, L., & Arnér, E. S. J. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.09.016 · Cited by 128
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The thioredoxin system and cancer therapy: a review
Mohammadi, F., Soltani, A., Ghahremanloo, A., Javid, H., & Hashemy, S. I. (2019) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-019-03912-4 · Cited by 127
Effect of selenium on rat thioredoxin reductase activity
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Redox Control in Mammalian Embryo Development
Ufer, C., Wang, C. C., Borchert, A., Heydeck, D., & Kühn, H. (2010) · Antioxidants and Redox Signaling · doi:10.1089/ars.2009.3044 · Cited by 121
“5) owing to reduced proliferation of the inner cell mass (251).”
Molecular genetics of implantation in the mouse
Rinkenberger, J. L., Cross, J. C., & Werb, Z. (1997) · Developmental Genetics · doi:10.1002/(sici)1520-6408(1997)21:1 · Cited by 126
Henderson, B. E., & Pockley, A. G. (2010) · Journal of Leukocyte Biology · doi:10.1189/jlb.1209779 · Cited by 119
“Inactivation of the gene encoding Trx1 in mice causes early embryonic lethality [71], thereby revealing the importance of Trx for organismal homeostasis.”
Background
Metadata
- Authors
- Matsui, M., Oshima, M., Oshima, H., Takaku, K., Maruyama, T., Yodoi, J., & Taketo, M. M.
- Affiliations
- Kyoto University (JP)
- Venue
- Developmental Biology
- Publisher
- Elsevier BV
- Published
- 1996-08
- Volume
- 178
- Issue
- 1
- Pages
- 179-185
- ISSN
- 0012-1606 (ISSN-L)
- OpenAlex
- W1991387227
- Cited by
- 546
- References
- 0
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 7 · 2023: 15 · 2022: 16 · 2021: 12 · 2020: 10 · 2019: 18 · 2018: 13 · 2017: 22 · 2016: 14 · 2015: 24 · 2014: 26 · 2013: 18 · 2012: 25
- FWCI
- 3.41
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Reproductive Medicine › Reproductive Biology and Fertility
- Keywords
- thioredoxin, targeted gene disruption, mouse embryo, early embryonic lethality, preimplantation embryo, inner cell mass, embryo resorption, gastrulation, embryonic morphogenesis, embryonic differentiation
- MeSH terms
- Animals, Blastocyst, Cell Division, Decidua, Female, Embryonic and Fetal Development, Genes, Homozygote, Organ Culture Techniques, Phenotype, Thioredoxins, Mice, Knockout, Gene Targeting, Mice
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