the role of thioredoxin reductases in brain development在大脑发育的作用硫氧还蛋白还原酶.pdfVIP

The Role of Thioredoxin Reductases in Brain Development 1 1 5 ¨ 2 ¨ 1 4 Jonna Soerensen , Cemile Jakupoglu , Heike Beck , Heidi Forster , Jorg Schmidt , Wolfgang Schmahl , Ulrich Schweizer3, Marcus Conrad2., Markus Brielmeier 1.* ¨ 1 Department of Comparative Medicine, Helmholtz Zentrum Munchen German Research Center for Environmental Health, Neuherberg, Germany, 2 Institute of Clinical ¨ Molecular Biology and Tumour Genetics, Helmholtz Zentrum Munchen German Research Center for Environmental Health, Munich, Germany, 3 AG Neurobiology of ´ ¨ Selenium, Neuroscience Research Center and Institute for Experimental Endocrinology, Charite-Universitatsmedizin, Berlin, Germany, 4 Institute of Veterinary Pathology, Chair of General Pathology Neuropathology, Ludwig-Maximilians University, Munich, Germany, 5 Institute of Physiology and Walter-Brendel Center, Ludwig-Maximilians University, Munich, Germany Abstract The thioredoxin-dependent system is an essential regulator of cellular redox balance. Since oxidative stress has been linked with neurodegenerative disease, we studied the roles of thioredoxin reductases in brain using mice with nervous system (NS)-specific deletion of cytosolic (Txnrd1) and mitochondrial (Txnrd2) thioredoxin reductase. While NS-specific Txnrd2 null mice develop normally, mice lacking Txnrd1 in the NS were significantly smaller and displayed ataxia and tremor. A striking patterned cerebellar hypoplasia was observed. Proliferation of the external granular layer (EGL) was strongly reduc