IDENTIFICATION OF THE FUNCTION OF GENES MUTETED IN X-LINKED MENTAL RETARDATION

Human Mental Retardation (MR) is a common and highly heterogeneous paediatric disorder with a very severe social impact. Although in the last 10 years a number of genes have been discovered whose mutations cause mental retardation, we are still far away from the identification of the consequence of these mutations on brain functions. With this project, using genetic and proteomic approaches in combination with molecular biology and behavioural studies, we aim to characterize the function of two genes (IL1RAPL1 and TM4SF2) whose mutations cause severe forms of X-linked non syndromic mental retardation. For this purpose we will use cell cultures and animal models of the diseases in order to: 1) identify the role of the two genes on brain synapse structure and function, 2) discover which genes and proteins are differentially modified the in brain of animals lacking these genes (knock-out animals) after specific cognitive tests, and 3) characterize the behavioural and cognitive deficits in KO animals. The study of these genes will not only help to better understand the molecular mechanisms of synapse formation and plasticity as well as learning and memory processes, but it will also open the possibility of future therapeutic approaches for such invalidating neuronal pathologies.