The Wilms’ tumour suppressor gene WT1, encodes a structurally diverse and multifunctional protein with tightly controlled expression throughout the development of several organ systems. Although initially defined as a tumor suppressor, WT1 has been found to be overexpressed in some cancers. How WT1 contributes to the shift from normal to aberrant development, or from normal function to oncogenic function, is poorly understood. Recent studies have shown an abundance of bidirectional transcription across metazoan genomes suggesting that non-coding antisense transcripts may have important roles in cell function. WT1-AS transcripts are capable of positively modulating WT1 protein levels in vitro, but relatively little is known about the functions of these antisense transcripts in vivo. The aim of this thesis was to characterize the role of a highly conserved region, Mcr2, located upstream of human and mouse WT1. Our data suggests that Mcr2 is not translated into protein and is transcribed in an antisense orientation. Mcr2 was found partially conserved in fish and well conserved in terrestrial vertebrates. By analysing novel mouse strains with genetically modified Mcr2 we have identified that Mcr2 may have a role in both fertility and embryonic survival, as well as regulating liquid homeostasis in the adult mouse.
|Date of Award||1 Sep 2010|
|Supervisor||Andrew Ward (Supervisor) & Kim Moorwood (Supervisor)|