title: A novel model of demyelination and remyelination in a GFP-transgenic zebrafish.
abstract: Demyelinating diseases consist of a variety of autoimmune conditions in which the myelin sheath is damaged due to genetic and/or environmental factors. During clinical treatment, some patients undergo partial remyelination, especially during the early disease stages. However, the mechanisms that regulate demyelination remain unclear. The myelin structure, myelin formation and myelin-related gene expression are highly conserved between mammals and zebrafish. Therefore, the zebrafish is an ideal model organism to study myelination. In this study, we generated a transgenic zebrafish Tg(mbp:nfsB-egfp) expressing a fusion protein composed of enhanced green fluorescent protein (EGFP) and NTR from the myelin basic protein (mbp) promoter. Tg(mbp:nfsB-egfp) expressed NTR-EGFP reproducibly and hereditarily in oligodendrocytes along the spinal cord. Treatment of zebrafish larvae Tg(mbp:nfsB-egfp) with metronidazole (Mtz) resulted in the selective ablation of oligodendrocytes and led to demyelination, accompanied by behavioral changes, including decreased total movement distance, velocity, total movement time and fast movement time. After withdrawal of Mtz for a seven day recovery period, the expression of EGFP and MBP protein was observed again which indicates remyelination. Additionally, locomotor capacity was restored. Collectively, Tg(mbp:nfsB-egfp), a heritable and stable transgenic line, provides a novel, powerful tool to study the mechanisms of demyelination and remyelination.
authors.affiliation: Key Laboratory of Tumor Microenviroment and Neurovascular Regulation, Nankai University School of Medicine, Tianjin 300071, China.
authors.forename: Yangwu
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Key Laboratory of Tumor Microenviroment and Neurovascular Regulation, Nankai University School of Medicine, Tianjin 300071, China.
authors.forename: Xudan
authors.initials: X
authors.lastname: Lei
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Science, Nankai University, Tianjin 300071, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Tumor Microenviroment and Neurovascular Regulation, Nankai University School of Medicine, Tianjin 300071, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Key Laboratory of Tumor Microenviroment and Neurovascular Regulation, Nankai University School of Medicine, Tianjin 300071, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Science, Nankai University, Tianjin 300071, China xzfeng@nankai.edu.cn weishihui706@hotmail.com liyuhao@nankai.edu.cn.
authors.forename: Xizeng
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Ophthalmology, Chinese PLA General Hospital, Beijing 100853, China xzfeng@nankai.edu.cn weishihui706@hotmail.com liyuhao@nankai.edu.cn.
authors.forename: Shihui
authors.initials: S
authors.lastname: Wei
authors.affiliation: Key Laboratory of Tumor Microenviroment and Neurovascular Regulation, Nankai University School of Medicine, Tianjin 300071, China xzfeng@nankai.edu.cn weishihui706@hotmail.com liyuhao@nankai.edu.cn.
authors.forename: Yuhao
authors.initials: Y
authors.lastname: Li
keywords: Demyelination; Myelin basic protein; Oligodendrocyte; Remyelination; Transgenic zebrafish