title: RNF8 deficiency results in neurodegeneration in mice.
abstract: The progressive loss of neurons causes neurodegenerative diseases. Because the accumulation of DNA breaks results in neuronal apoptosis, the lack of a variety of DNA damage repair-related proteins contributes to neurodegeneration. The ubiquitin ligase RNF8 plays an important role in DNA double-strand break repair via histone ubiquitination. However, the function of RNF8 in terminally differentiated neurons remains unknown. This study aimed to determine whether RNF8 is involved in the DNA damage response in neurons and contributes to neurodegeneration. Here, we present evidence suggesting that RNF8 deficiency results in DNA damage accumulation and neuronal apoptosis. RNF8(-/-) mice exhibit neuronal degeneration and reactive astrocytosis. Neurons from RNF8(-/-) mice appear to be more susceptible to X-ray-induced DNA damage. These changes were consistent with the behavioral performances of the RNF8-deficient mice, which included impaired performances in the open-field test and step-down avoidance task. Overall, these findings show that RNF8 is required for DNA damage repair in neurons. RNF8 deficiency is sufficient to cause neuronal pathology and cognitive decline, and the loss of RNF8 results in neuron degeneration.
authors.affiliation: Department of Anatomy and Histology, Lanzhou University School of Basic Medical Sciences, Lanzhou, 730000, China.|Department of Anatomy, Northwest University for Nationalities School of Medicine, Lanzhou, 730030, China.
authors.forename: Siwei
authors.initials: S
authors.lastname: Ouyang
authors.affiliation: Department of Anatomy and Histology, Lanzhou University School of Basic Medical Sciences, Lanzhou, 730000, China.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Anatomy and Histology, Lanzhou University School of Basic Medical Sciences, Lanzhou, 730000, China.
authors.forename: Yingxia
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Internal Medicine, The University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Yibin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, The University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Anatomy and Histology, Lanzhou University School of Basic Medical Sciences, Lanzhou, 730000, China.
authors.forename: Degui
authors.initials: D
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002478:Cells, Cultured; D003072:Cognition Disorders / Q000235:genetics; D004247:DNA / Q000235:genetics*; D053960:DNA Breaks / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics*; D006657:Histones / Q000378:metabolism; D051379:Mice; D019636:Neurodegenerative Diseases / Q000235:genetics*; D009474:Neurons / Q000473:pathology; D044767:Ubiquitin-Protein Ligases / Q000172:deficiency / Q000502:physiology*; D054875:Ubiquitination
chemical_list: D006657:Histones; D004247:DNA; C549817:Rnf8 protein, mouse; D044767:Ubiquitin-Protein Ligases
keywords: DNA damage repair; Double-strand break; Neurodegeneration; RNF8; Ubiquitin ligase