Molecular studies of the circadian control candidate genes in the mouse Smith-Magenis syndrome syntenic region.

• Main Author: Chen, Ken Shiung.
• Other Authors: School of Biological Sciences
• Format: Research Report
• Language: English
• Published: 2010
• Subjects: DRNTU::Science::Biological sciences::Molecular biology
• Online Access: http://hdl.handle.net/10356/41874
• Institution: Nanyang Technological University

The Smith-Magenis syndrome (SMS) is a contiguous gene syndrome which is associated with the deletion in chromosome 17 p11.2. The common clinical features of SMS patients include mental retardation, delayed speech and motor development, behavior problems, sleep disturbance, minor craniofacial abnormalities, short stature, and brachydactyly. Recent works in circadian clock have addressed possible molecular links between the endogenous circadian clock and cell cycle regulation. One of the interesting phenotype Associated with SMS is sleep disturbance. RASDl and RAIl are located in the SMS critical region and have, recently, been implicated in contributing to the sleep disturbance phenotypes in SMS. In this proposal, we aim to determine the cellular roles of these two genes by identifying the interacting proteins and studying the transcription regulatory elements. Thymine DNA glycosylase (Tdg) and angiogenic factor with G-patch and FHA domain (Iggfl) were identified as Rail interacting proteins while NonD and. Tubb5 were identified as Rasd1 interacting protein. Furthermore, we have identified functional retinoic acid receptors binding site in the Rail promoter first intron region and functional glucocorticoid response element (GRE) consensus sequence ~2kb downstream of Rasdl.