Browsing by Author "Mariano, Sara Isabel Lima Silva Morais"
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- Zebrafish as a model to study brain pathologies associated to mef2c mutations and haploinsufficiencyPublication . Mariano, Sara Isabel Lima Silva Morais; Conceição, Natércia; Vitorino, MartaThe MRD20 syndrome is caused by an haploinsu ciency of the MEF2C gene. This disease causes patients to display mental retardation, absence of speech, limited walking abilities, and is considered one of the main causes of intellectual disability. MEF2C belongs to the MEF2 family of transcription factors, which is crucial for cell development and di erentiation, but unlike other MEF2 proteins, MEF2C is restricted to muscle, brain and spleen. Zebra sh possesses two copies of the mef2c gene: mef2ca and mef2cb, and in this study we used one mutant line for each of the gene. The main concern in this work was to analyse whether zebra sh is able to model mef2c haploinsu ciency using the zebra sh mutants. First, we analysed the syntenic arrangement of the genes surrounding mef2c and concluded that the pattern of neighbouring genes is conserved among di erent species. Following a previous work we investigated the putative binding of Mef2c to mecp2 promoter. However, no e ects were detected in the mecp2 promoter by Mef2ca and Mef2cb, alone or together, suggesting that there may lacking co-factors for this binding to occur. In order to understand if mef2c mutations cause impairment in locomotion or memory, we performed locomotor and learning experiments in zebra sh mutants. The results showed a decrease in coiling activity, an increase in covered distance and activity percentage from mutants to the WT larvae. In the memory tests we found some di erences between mutants and the WT sh. We further explored the expression of putative Mef2c target genes in Mef2c mutant zebra sh using quantitative polymerase chain reaction. Our results suggested that emx1 was highly expressed in mef2cb heterozygous mutants, suggesting an impairment of the telencephalon. These observations suggest that zebra sh Mef2c mutant sh, serve as good animal models to study the mef2c haploinsu ciency.