Investigating the context effects of expanded hexanucleotide repeats in fly model of human SCA 36.
Abstract: SCA 36 (Spinocerebellar Ataxia 36) is a neurodegenerative disorder that is caused by a GGCCTG hexanucleotide repeat expansions in NOP56 gene in the intronic region. SCA 36 is characterized by gait ataxia, abnormal eye movements, hearing loss and motor neuron impairment. To examine the potential pathogenic mechanisms that lead to SCA 36, We have generated fly models of this disease by expressing DNA fragments with up to 100 pure GGCCTG repeats within different sequence contexts and with different reporter tags in fruit flies. Transgenic flies made from these vectors and the transgenic flies with the expanded repeats were crossed with specific drivers for gene expression. The nervous system-associated phenotypes were analyzed. We found that the pure repeats in the exonic region can cause rough eye phenotype, a characteristic phenomenon in fly models of neurodegenerative diseases. Our results suggest that the GGCCTG hexanucleotide repeats themselves can be toxic even without the context of NOP56. These studies will help to better understand the underlying mechanism of SCA36 diseases and towards the end find the targets towards effective intervention of this disease.
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