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Expression pattern of cdkl5 during zebrafish early development: implications for use as model for atypical Rett syndrome

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Atypical Rett syndrome is a child neurodevelopmental disorder induced by mutations in CDKL5 gene and characterized by a progressive regression in development with loss of purposeful use of the hands, slowed brain and head growth, problems with walking, seizures, and intellectual disability. At the moment, there is no cure for this pathology and little information is available concerning animal models capable of mimicking its phenotypes, thus the development of additional animal models should be of interest to gain more knowledge about the disease. Zebrafish has been used successfully as model organism for many human genetic diseases; however, no information is available concerning the spatial and temporal expression of cdkl5 orthologous in this organism. In the present study, we identified the developmental expression patterns of cdkl5 in zebrafish by quantitative PCR and whole-mount in situ hybridization. cdkl5 is expressed maternally at low levels during the first 24 h of development. After that the expression of the gene increases significantly and it starts to be expressed mainly in the nervous system and in several brain structures, such as telencephalon, mesencephalon and diencephalon. The expression patterns of cdkl5 in zebrafish is in accordance with the tissues known to be affected in humans and associated to symptoms and deficits observed in Rett syndrome patients thus providing the first evidence that zebrafish could be an alternative model to study the molecular pathways of this disease as well as to test possible therapeutic approaches capable of rescuing the phenotype.

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This research was partially supported by national funds from FCT - Foundation for Science and Technology through project UID/Multi/04326/2013. MV was supported by a postdoctoral fellowship reference SFRH/BPD/65923/2009 from the Portuguese Foundation for Science and Technology (FCT).

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Correspondence to Marta Vitorino.

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The authors declare that they have no conflict of interest.

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All experimental procedures involving animals followed the European Directive 2010/63/EU and the related guidelines (European Commission, 2014) and Portuguese legislation (Decreto-Lei 113/2013 and Despacho 2880/2015) for animal experimentation and welfare.

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Vitorino, M., Cunha, N., Conceição, N. et al. Expression pattern of cdkl5 during zebrafish early development: implications for use as model for atypical Rett syndrome. Mol Biol Rep 45, 445–451 (2018).

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