Zebrafish (Danio rerio, Hamilton‐Buchanan, 1822) as a model to study bone diseases associated with Rett syndrome

Summary Rett syndrome (RTT) is a severe neurological disorder in humans that almost exclusively affects only females. This disease is characterized by an apparent normal growth and intellectual development during the first year of life, followed by a progressive regression in development characterized by loss of purposeful use of the hands, distinctive hand movements, slowed brain and head growth, problems with walking, seizures, and intellectual disability. Mutations in the X‐linked gene methyl‐CpG‐binding protein 2 (MECP2) were described in RTT patients. Several bone diseases related with decreased bone mass starting early in life were recently ascribed to RTT. Because the zebrafish was largely validated as a model for human genetic diseases, the main objective of this work was to investigate whether zebrafish could be a good model to study bone diseases associated with RTT. For this purpose, first compared were zebrafish and human MECP2 regarding their chromosomal environment, gene structure, and protein conservation. In silico analysis showed a similar genetic structure for zebrafish mecp2 and its human ortholog, and both species present spliced isoforms. Zebrafish and human MECP2 promoter regions present similar putative binding sites for known transcription factors that affect both neural and bone metabolisms. Protein bioinformatic analysis showed a high degree of conservation between zebrafish and human, particularly in the functional domains of both proteins. In conclusion, this study demonstrates that the zebrafish has the appropriate genetic characteristics for further consideration as a model to investigate the bone diseases associated with Rett syndrome.