Zebrafish (Danio rerio) are tropical freshwater fish and a vertebrate model organism that is used to study vertebrate development because of transparent embryos, and rapid and external development. Especially, zebrafish have been extensively used to research nervous system development and to establish vertebrate models of neurodegenerative diseases [21, 22]. Zebrafish have astrocytes [23], and zebrafish Gfap shares 67% identity and 77% similarity with human GFAP, along with well-conserved hot spot amino acids mutated in AxD (Fig. 1a) [24]. In addition, regulatory elements that drive the specific expression of zebrafish gfap in astrocytes were identified [25].
Fig. 1 Clinical features and GFAP sequences of the proband. a Comparison between human and zebrafish GFAP, and location of amino acid residues whose mutations are discussed in this study. Human GFAP: NCBI accession number NP_002046; zebrafish Gfap: NP_571448. D: aspartate; R: arginine. b Pedigree of individuals with p.Asp128Asn GFAP shown as solid symbols. Symbols and nomenclature follow established guidelines [44]. A small circle within a square or a circle indicates an individual who tested negative for a GFAP mutation. P, proband. c-e Brain MR images of the proband. c Sagittal T2-weighted MR image shows marked atrophy of the medullar oblongata (arrow). d Sagittal T1-weighted MR image reveals prominent atrophy in the upper cervical cord (arrow) and cerebellar hemisphere (arrowhead). e Fluid-attenuated inversion recovery (FLAIR) image shows high signal intensity lesions in the bilateral cerebellar dentate nuclei (arrow). f and g DNA sequence analysis of the GFAP. Arrows indicate c.382G. f Electropherogram of the proband reveals a heterozygous G-to-A substitution at position 382 of the GFAP, which is predicted to substitute asparagine for aspartic acid (p.Asp128Asn). g Representative electropherogram of GFAP sequences in 200 control subjects