Project 461314

This research project that uses genetic mouse models of the epigenetic enzymes MLL4 and UTX to determine how mutations in these genes give rise to muscle weakness (hypotonia) in children with Kabuki Syndrome. We have characterized mice with mutations in each of these proteins, and found that the muscle stem cells responsible for building and repairing the muscle are very inefficient at generating new muscle fibres. We are exploiting these mouse systems to identify the mechanisms disrupted in these stem cells that prevent efficient repair of the muscle. Thus, the knowledge gained from these studies will be important to the development of new therapies to treat hypotonia in Kabuki Syndrome. Furthermore, as Kabuki Syndrome is a multi-system disease that remains poorly understood for all affected tissues, our strong muscle phenotype observed in mutant mice will allow us to provide the first insight into the disease mechanism with the hope it will help understand the disease progression in other tissues.