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Publication : Minimal role for activating transcription factor 3 in the oligodendrocyte unfolded protein response in vivo.

First Author  Sharma R Year  2007
Journal  J Neurochem Volume  102
Issue  5 Pages  1703-12
PubMed ID  17697053 Mgi Jnum  J:124894
Mgi Id  MGI:3722743 Doi  10.1111/j.1471-4159.2007.04646.x
Citation  Sharma R, et al. (2007) Minimal role for activating transcription factor 3 in the oligodendrocyte unfolded protein response in vivo. J Neurochem 102(5):1703-12
abstractText  To further our goal of identifying and characterizing the functions of major components of the unfolded protein response (UPR) in oligodendrocytes, the gene encoding the activator of transcription factor 3 protein (ATF3) has been ablated in mice expressing mutant forms of the Proteolipid protein 1 (Plp1) gene and the phenotype of double mutants characterized at several levels. Mature oligodendrocytes in Plp1 mutant mice undergo UPR-induced cell stress, induce ATF3 expression and exhibit a greater propensity to die by apoptosis, which is consistent with pro-death function of ATF3 proposed from in vitro studies. However, we find that the absence of ATF3 has no effect on the levels of apoptosis in Plp1 mutants. Furthermore, we find that oligodendrocyte function appears normal in Atf3(-/-) mice and that motor coordination and neural communication are similarly unaffected. Accordingly, we conclude that ATF3, at best, plays a minor role in UPR signaling and its expression is more likely induced by the UPR as a secondary event in oligodendrocytes that is unrelated to cell death.
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