Cytoplasmic thioredoxin reductase is essential for embryogenesis but dispensable for cardiac development.
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.
Jakupoglu
Cemile
C
Department of Comparative Medicine, Institute of Clinical Molecular Biology and Tumor Genetics, GSF, Marchioninistr. 25, D-81377 Munich, Germany.
Przemeck
Gerhard K H
GK
Schneider
Manuela
M
Moreno
Stéphanie G
SG
Mayr
Nadja
N
Hatzopoulos
Antonis K
AK
de Angelis
Martin Hrabé
MH
Wurst
Wolfgang
W
Bornkamm
Georg W
GW
Brielmeier
Markus
M
Conrad
Marcus
M
D000818:Animals; D003593:Cytoplasm / Q000378:metabolism; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000737:chemistry / Q000166:cytology; D047108:Embryonic Development; D015870:Gene Expression; D018390:Gene Targeting; D006321:Heart / Q000196:embryology*; D051379:Mice; D009206:Myocardium / Q000737:chemistry / Q000166:cytology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D054481:Thioredoxin Reductase 1; D054482:Thioredoxin Reductase 2; D013880:Thioredoxin-Disulfide Reductase / Q000032:analysis / Q000235:genetics / Q000502:physiology*
D012333:RNA, Messenger; D054481:Thioredoxin Reductase 1; D054482:Thioredoxin Reductase 2; D013880:Thioredoxin-Disulfide Reductase; C516125:Txnrd1 protein, mouse; C516128:Txnrd2 protein, mouse