Journal article
Effects of thioredoxin reductase-1 deletion on embryogenesis and transcriptome
Free radical biology & medicine, Vol.43(6), pp.911-923
2007
Handle:
https://hdl.handle.net/2376/103685
PMCID: PMC2099259
PMID: 17697936
Abstract
Thioredoxin reductases (Txnrd) maintain intracellular redox homeostasis in most organisms. Metazoan Txnrds also participate in signal transduction. Mouse embryos homozygous for a targeted null mutation of the
txnrd1 gene, encoding the cytosolic thioredoxin reductase, were viable at embryonic day 8.5 (E8.5) but not at E9.5. Histology revealed that
txnrd1
−/− cells were capable of proliferation and differentiation; however, mutant embryos were smaller than wild-type littermates and failed to gastrulate. In situ marker gene analyses indicated that primitive streak mesoderm did not form. Microarray analyses on E7.5
txnrd
−/− and
txnrd
+/+ littermates showed similar mRNA levels for peroxiredoxins, glutathione reductases, mitochondrial Txnrd2, and most markers of cell proliferation. Conversely, mRNAs encoding sulfiredoxin, IGF-binding protein 1, carbonyl reductase 3, glutamate cysteine ligase, glutathione
S-transferases, and metallothioneins were more abundant in mutants. Many gene expression responses mirrored those in
thioredoxin reductase 1-null yeast; however, mice exhibited a novel response within the peroxiredoxin catalytic cycle. Thus, whereas yeast induce peroxiredoxin mRNAs in response to thioredoxin reductase disruption, mice induced sulfiredoxin mRNA. In summary, Txnrd1 was required for correct patterning of the early embryo and progression to later development. Conserved responses to Txnrd1 disruption likely allowed proliferation and limited differentiation of the mutant embryo cells.
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Details
- Title
- Effects of thioredoxin reductase-1 deletion on embryogenesis and transcriptome
- Creators
- Alla A Bondareva - VMB, Molecular Biosciences, 960 Technology Blvd., Montana State University, Bozeman, MT 59718, USAMario R Capecchi - Howard Hughes Medical Institute, Eccles Institute of Human Genetics, University of Utah, Salt Lake City, UT 84112, USASonya V Iverson - VMB, Molecular Biosciences, 960 Technology Blvd., Montana State University, Bozeman, MT 59718, USAYan Li - VMB, Molecular Biosciences, 960 Technology Blvd., Montana State University, Bozeman, MT 59718, USANathan I Lopez - Biochemistry and Biophysics Department, ALS2011, Oregon State University, Corvallis, OR 97331, USAOlivier Lucas - VMB, Molecular Biosciences, 960 Technology Blvd., Montana State University, Bozeman, MT 59718, USAGary F Merrill - Biochemistry and Biophysics Department, ALS2011, Oregon State University, Corvallis, OR 97331, USAJustin R Prigge - VMB, Molecular Biosciences, 960 Technology Blvd., Montana State University, Bozeman, MT 59718, USAAshley M Siders - VMB, Molecular Biosciences, 960 Technology Blvd., Montana State University, Bozeman, MT 59718, USAMaki Wakamiya - Department of Neurology, UTMB, Clay Hall Rm. 1.128, 301 University, Galveston, TX 77555, USAStephanie L Wallin - VMB, Molecular Biosciences, 960 Technology Blvd., Montana State University, Bozeman, MT 59718, USAEdward E Schmidt - VMB, Molecular Biosciences, 960 Technology Blvd., Montana State University, Bozeman, MT 59718, USA
- Publication Details
- Free radical biology & medicine, Vol.43(6), pp.911-923
- Academic Unit
- UNKNOWN
- Publisher
- Elsevier Inc
- Identifiers
- 99900546688301842
- Language
- English
- Resource Type
- Journal article