BACKGROUND

Methyl CpG binding protein 2 (MECP2) is an essential global modulator of transcription and mutations in MECP2 are the most common cause of Rett syndrome, an X-linked neurodevelopmental disorder. Patients diagnosed with Rett syndrome have increased risk for epilepsy as well as problems with anxiety and social communication. Using the zebrafish mecp2 line, this study aimed to increase our understanding of the role of Mecp2 function in regulation of pharmacologically-induced hyperlocomotion, developmental social preference, and adult socialization, anxiety-related behaviour, and baseline cortisol levels. To determine responses of mecp2 zebrafish to a stimulating convulsant, general locomotor activity was measured at 5 days post-fertilization (dpf) in sibling mecp2, mecp2, and mecp2 fish after treatment with a GABA receptor antagonist pentylenetetrazol (PTZ) at varying concentrations. Responses to social stimulus were investigated in juvenile (21 dpf) and adult mecp2 and mecp2 fish. Anxiety responses to a novel tank and whole-body cortisol levels were also measured in adult mecp2 and control mecp2 zebrafish.

RESULTS

The behavioural tests showed that mecp2 zebrafish displayed hypolocomotion at the larval stage, along with increased freezing time and thigmotaxis, and higher whole-body cortisol levels in adulthood. However, the hyper-locomotion response to PTZ at 5 dpf and social preference for visual social stimulus at 21 dpf and in adulthood were not affected by the lack of functional Mecp2.

CONCLUSIONS

Functional Mecp2 modulated larval locomotion and behavioural anxiety at different ages and adult cortisol levels, but mecp2 null-mutation did not alter adult locomotion and socialization, and developmental sociability and PTZ-induced hyperlocomotion in zebrafish. Given the variability reported in patients and in rodent Mecp2 knockout models, studies using zebrafish can explore vital elements of MECP2's role across development and improve our understanding of neural mechanisms underlying neurodevelopmental disorders.