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Brain vs. Gut: Differential Expression of Shank3 Isoforms in Zebrafish
Location: 42
Mentor: Dr. Julia Dallman
Shank3 is a scaffolding protein important for brain development and is expressed in intestinal enterochromaffin cells (EECs), suggesting a role in gut motility. The full-length Shank3 protein binds many proteins for signal transduction, but several protein isoforms result from alternative splicing. Although the isoforms of Shank3 are differentially expressed throughout development, their exact roles are unknown. Haploinsufficiency of the SHANK3 gene has been linked to Phelan-McDermid Syndrome (PMS), a type of autism, and causes some of the symptoms. The highly conserved nature of SHANK3 allows zebrafish to be used as model animals in autism research. However, unlike other model animals, zebrafish have two copies of shank3. We hypothesized that the two genes code for different protein isoforms that are differentially expressed in the brains and guts of zebrafish. To examine the role of the isoforms and better understand zebrafish, genetic differences in the alternative splicing of the shank3a and shank3b genes were studied. Results indicated that there was greater variety in the alternative splicing of shank3a, with differences being distributed throughout most of the gene. Differences among shank3b isoforms were largely concentrated in the exons encoding the proline-rich region near the C-terminus of the protein. These results indicate a difference in the roles of the two genes in zebrafish and will improve future autism models. Future research will include using these results for PCR and gel electrophoresis to determine the differential expression of the isoforms in the brains and guts and to determine their functions.
