Cytoplasmic Thioredoxin Reductase is Essential for Embryogenesis but Dispensable for Cardiac Development

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2005 Feb 17

PMID 15713651

Citations 144

Authors

Cemile Jakupoglu

Gerhard K H Przemeck

Manuela Schneider

Stephanie G Moreno

Nadja Mayr

Antonis K Hatzopoulos

Martin Hrabe de Angelis

Wolfgang Wurst

Georg W Bornkamm

Markus Brielmeier

Marcus Conrad

Affiliations

Soon will be listed here.

Abstract

Two distinct thioredoxin/thioredoxin reductase systems are present in the cytosol and the mitochondria of mammalian cells. Thioredoxins (Txn), the main substrates of thioredoxin reductases (Txnrd), are involved in numerous physiological processes, including cell-cell communication, redox metabolism, proliferation, and apoptosis. To investigate the individual contribution of mitochondrial (Txnrd2) and cytoplasmic (Txnrd1) thioredoxin reductases in vivo, we generated a mouse strain with a conditionally targeted deletion of Txnrd1. We show here that the ubiquitous Cre-mediated inactivation of Txnrd1 leads to early embryonic lethality. Homozygous mutant embryos display severe growth retardation and fail to turn. In accordance with the observed growth impairment in vivo, Txnrd1-deficient embryonic fibroblasts do not proliferate in vitro. In contrast, ex vivo-cultured embryonic Txnrd1-deficient cardiomyocytes are not affected, and mice with a heart-specific inactivation of Txnrd1 develop normally and appear healthy. Our results indicate that Txnrd1 plays an essential role during embryogenesis in most developing tissues except the heart.

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