title: Minimal role for activating transcription factor 3 in the oligodendrocyte unfolded protein response in vivo.
abstract: 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.
authors: Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan, USACarman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, Michigan, USADepartment of Neurology, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors: Ramaswamy
authors: R
authors: Sharma
authors: Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan, USACarman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, Michigan, USADepartment of Neurology, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors: HuiYuan
authors: H
authors: Jiang
authors: Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan, USACarman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, Michigan, USADepartment of Neurology, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors: Laura
authors: L
authors: Zhong
authors: Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan, USACarman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, Michigan, USADepartment of Neurology, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors: James
authors: J
authors: Tseng
authors: Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan, USACarman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, Michigan, USADepartment of Neurology, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors: Alexander
authors: A
authors: Gow
mesh_terms: D051700:Activating Transcription Factor 3 / Q000235:genetics / Q000378:metabolism*; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000235:genetics; D001522:Behavior, Animal; D005786:Gene Expression Regulation / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000502:physiology; D018991:Myelin Proteolipid Protein / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism*
chemical_list: D051700:Activating Transcription Factor 3; C103002:Atf3 protein, mouse; D018991:Myelin Proteolipid Protein; D009419:Nerve Tissue Proteins; C047516:Plp1 protein, mouse