Özet:
Characterized by deficits in both intellectual ability and adaptive behavior, intellectual disabilities (IDs) are one of the major neurodevelopmental disorders with a prevalence of 1- 3% worldwide. Development of Next Generation Sequencing techniques provided an important step for the study of ID and identification of ID-related genes. A whole exome sequencing study of 404 consanguineous families with ID led to the identification of a novel ID-related missense variant (cT1150C; p.C384R) in the RNFT2 gene. RNFT2 (RING finger protein, transmembrane 2) encodes a RING finger E3 ubiquitin ligase. Its fly ortholog Dmel/CG13605 has the same type of RING finger domain (C3HC4) and is predicted to be a ubiquitin E3 ligase. The aim of this study is to characterize the fly orthologue of RNFT2, CG13605, and investigate the role of RNFT2 in ID and the orthology between two proteins. For this aim, first I investigated the expression pattern of CG13605 and observed expression in the mushroom body (MB) Kenyon cells throughout development. Then I conducted loss of function experiments by RNAi knockdown and generating and investigating CRISPR knockout mutants. Knockdown experiments resulted in misguidance defects in the MB lobes. Similarly, knockout experiments also led to various MB phenotypes in α/β lobes. To investigate the orthology between RNFT2 and CG13605, I expressed transgenic wild type and mutant RNFT2 in flies in the CG13605 mutant background. Rescue experiments with wild type RNFT2 resulted in rescue of observed phenotypes, indicating a function- oriented orthology between RNFT2 and CG13605.
