Nielsen Anders Lade, Jørgensen Arne Lund
Department of Human Genetics, The Bartholin Building, University of Aarhus, DK-8000, Aarhus C, Denmark.
Gene. 2003 May 22;310:123-32. doi: 10.1016/s0378-1119(03)00526-2.
Glial fibrillary acidic protein, GFAP, is an astrocyte-specific member of the family of intermediate filament proteins which are involved in formation of the cytoskeletal structure. We here present a characterization of the zebrafish GFAP gene and corresponding protein. The zebrafish GFAP gene have the same exon-intron organization as the mammalian orthologoue genes. Comparison of the protein with mammalian GFAP shows that the amino acid sequence is highly conserved in the rod and tail domains whereas the head domain has diverged. Zebrafish GFAP exhibits functional characteristics of an intermediate filament protein such as dimerization potential, capacity to assembly into filaments, and cytoskeletal localization. Mutations in human GFAP have been associated with a severe childhood brain disorder called Alexander disease. Interestingly, the mutations affect preferentially amino acid residues of GFAP that are evolutionarily conserved. This indicates that a change of functionally core residues in GFAP is a prerequisite for the disease phenotype to develop and the initial steps in the pathogenesis may thus be modeled in zebrafish.
胶质纤维酸性蛋白（GFAP）是中间丝蛋白家族中一种星形胶质细胞特异性成员，该家族参与细胞骨架结构的形成。我们在此展示斑马鱼GFAP基因及相应蛋白的特征。斑马鱼GFAP基因具有与哺乳动物直系同源基因相同的外显子-内含子组织。将该蛋白与哺乳动物GFAP进行比较表明，其氨基酸序列在杆状结构域和尾部结构域高度保守，而头部结构域则有所不同。斑马鱼GFAP表现出中间丝蛋白的功能特征，如二聚化潜力、组装成丝的能力以及细胞骨架定位。人类GFAP中的突变与一种名为亚历山大病的严重儿童脑部疾病有关。有趣的是，这些突变优先影响GFAP中进化上保守的氨基酸残基。这表明GFAP中功能核心残基的改变是疾病表型发展的先决条件，因此发病机制的初始步骤可能可以在斑马鱼中进行模拟。
