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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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“The importance of thioredoxin is supported by the findings that gene knockout in mice is embryonically lethal [4].”
BackgroundMithen, R. F. (2007) · International Journal for Vitamin and Nutrition Research · doi:10.1024/0300-9831.77.3.205 · Cited by 13
“For example, knockout of thioredoxin reductase is lethal in embryos [37], knockout of cytosolic glutathione peroxidase increases sensitivity to oxidative stress, and knockout of DIO2 results in abnormal neurological development [38].”
BackgroundThioredoxin in the Endocrine Response to Stress
Tanaka, H., Makino, Y., & Okamoto, K. (1997) · Vitamins and hormones · doi:10.1016/s0083-6729(08)60643-3 · Cited by 14
Insights into the Multifaceted Roles of Thioredoxin-1 System: Exploring Knockout Murine Models
Shcholok, T., & Eftekharpour, E. (2024) · Biology · doi:10.3390/biology13030180 · Cited by 13
“Global inborn Trx-1 deletion is reported to be embryonically lethal [1].”
BackgroundOxidation-Induced Mixed Disulfide and Cataract Formation: A Review
Lou, M. F., & Augusteyn, R. C. (2025) · Antioxidants · doi:10.3390/antiox14040425 · Cited by 13
“TRx gene expression is essential for early differentiation and morphogenesis of embryos; thus, the deletion of this gene is lethal [84].”
Oxidation Pathways and Plant Development: Crosstalk between Thioredoxin and Glutaredoxin Pathways
Eckardt, N. A. (2007) · The Plant Cell · doi:10.1105/tpc.107.054270 · Cited by 13
“In mouse, disruption of the unique gene encoding the cytosolic TRX leads to early embryonic lethality (Matsui et al., 1996), and disruption of the gene encoding the mitochondrial NTR impairs embryo development due to severe retardation of growth and/or cardiac development (Jakupoglu et al., 2005).”
BackgroundHostetler, C. E., Michal, J. J., Robison, M., et al. (2006) · Journal of Animal Science · doi:10.2527/jas.2005-372 · Cited by 13
“Lack of thioredoxin is embryonically lethal because many transcription factors require thioredoxin reduction for DNA binding (Matsui et al., 1996).”
BackgroundLin, M., Bao, C., Chen, L., Geng, S., Wang, H., Xiao, Z., Gong, T., Ji, C., & Cheng, B. (2023) · Photochemical & Photobiological Sciences · doi:10.1007/s43630-023-00450-0 · Cited by 14
“TXNs are potent antioxidants that underlie cell proliferation and apoptosis in various organs [30].”
Mechanistic Role of Thioredoxin 2 in Heart Failure.
Chen, C.-F., Chen, H., Zhou, H., Ji, W.-D., & Min, W. (2017) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-319-55330-6_14 · Cited by 11
Chapter 9 Redundancy and Crosstalk Within the Thioredoxin and Glutathione Pathways
Reichheld, J., Bashandy, T., Siala, W., Riondet, C., Delorme‐Hinoux, V., Meyer, A. J., & Meyer, Y. (2009) · Advances in botanical research · doi:10.1016/s0065-2296(10)52009-3 · Cited by 12
“Inactivation of Trx1 (Matsui et al., 1996) or TrxR1 (Jakupoglu et al.”
BackgroundThe Impact of Oxidative Stress on Female Reproduction and ART: An Evidence-Based Review
Gupta, S., Sekhon, L. H., Aziz, N., & Agarwal, A. K. (2008) · Cambridge University Press eBooks · doi:10.1017/cbo9780511547287.067 · Cited by 12
The Role of Oxidative Stress in Female Reproduction and Pregnancy
Lzr, L. (2012) · InTech eBooks · doi:10.5772/32515 · Cited by 13
“Studies investigating the correlation between adrenal-4 binding protein (Ad4BP) and superoxide dismutase expression also suggest an association between oxidative stress and ovarian steroidogeneis (Matsui et al.,1996).”
BackgroundExpression of peroxiredoxins and thioredoxins in the mouse spinal cord during embryonic development
Pirson, M., & Knoops, B. (2015) · The Journal of Comparative Neurology · doi:10.1002/cne.23807 · Cited by 12
“Inactivation of Trx1 and Trx2 genes in transgenic mice leads to prenatal lethality, with Trx2 knockout embryos displaying an open anterior neural tube and a strong increase in cell death (Matsui et al., 1996; Nonn et al., 2003).”
BackgroundYang, H., Kang, M., Guo, X., et al. (2010) · Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology · doi:10.1016/j.cbpb.2010.04.003 · Cited by 12
Role of In Vivo Vascular Redox in Resistance Arteries
Hilgers, R. H. P., & Das, K. C. (2014) · Hypertension · doi:10.1161/hypertensionaha.114.04473 · Cited by 11
Yang, L., Zeng, C., Zhang, Y., Wang, F., Takamiya, M., & Strähle, U. (2019) · Toxicology Letters · doi:10.1016/j.toxlet.2019.07.009 · Cited by 11
Mitochondria and telomeres: hand in glove
Vaurs, M., Dolu, E. B., & Decottignies, A. (2023) · Biogerontology · doi:10.1007/s10522-023-10074-7 · Cited by 11
“Supporting a damaging role of ROS at a very early stage of the embryonic development, mice deficient for the thiore-doxin antioxidant protein do not develop to the blastocyst stage (Matsui et al. 1996).”
Nalvarte, I., Damdimopoulos, A. E., Rüegg, J., & Spyrou, G. (2015) · Bioscience Reports · doi:10.1042/bsr20150236 · Cited by 11
Ohmori, I., Ouchida, M., Imai, H., Ishida, S., Toyokuni, S., & Mashimo, T. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105921 · Cited by 18
“Homozygous Txn1 knockout mice are embryonically lethal, whereas heterozygous mice show normal development (Matsui et al., 1996).”
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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