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

Abstract

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.

Zebrafish in understanding molecular pathophysiology, disease modeling, and developing effective treatments for Rett syndrome

“…[79][80][81][82] In this respect, functional domains of human MECP2 and zebrafish mecp2 proteins and genomics studies indicate that zebrafish has emerged as an interesting species in reshaping our understanding of MECP2 mutations and clinical parameters impact bone mass in RTT and eventually will evaluate treatments against these human skeletal disorders. 25,79,83,84 A recent proteomic study using the mecp2 Q63X mutant (mecp2-null) zebrafish to examine protein expression changes in mecp2-null versus wild-type larvae and adult zebrafish showed that 20 proteins are differentially expressed between mutant and wild-type fish. 85 The identified proteins are involved in skeletal and cardiac muscle function and redox balance maintenance.…”