Affiliation:
1. Arizona Cancer Center, University of Arizona, Tucson, Arizona 85714-5024
Abstract
ABSTRACT
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.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Reference33 articles.
1. Andreassen, O. A., R. J. Ferrante, A. Dedeoglu, D. W. Alber, P. Klivenyi, E. J. Carlson, C. J. Epstein, and M. F. Beal. 2001. Mice with a partial deficiency of manganese superoxide dismutase show increased vulnerability to the mitochondrial toxins malone, 3-nitropropionic acid, and MPTP. Exp. Neurol. 167 : 189-195.
2. Asikainen, T. M., T. T. Huang, E. Taskinen, A. L. Levonen, E. Carlson, R. Lapatto, C. J. Epstein, and K. O. Raivio. 2001. Increased sensitivity of homozygous Sod2 mutant mice to oxygen toxicity. Free Radic. Biol. Med. 32 : 175-186.
3. Boveris, A. 1984. Determination of the production of superoxide radicals and hydrogen peroxide in mitochondria. Methods Enzymol. 105 : 429-435.
4. Bustamante, E., J. W. Sper, and P. L. Pedersen. 1977. A high-yield preparative method for isolation of rat liver mitochondria. Anal. Biochem. 80 : 401-408.
5. Chae, H. Z., H. J. Kim, S. W. Kang, and S. G. Rhee. 1999. Characterization of three isoforms of mammalian peroxiredoxin that reduce peroxides in the presence of thioredoxin. Diabetes Res. Clin. Pract. 45 : 101-112.
Cited by
372 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献