Development of new experimental models for mental retardation and autism by iPS technology: generation of human affected and animal model neurons by reprogramming skin fibroblasts and testing gene correction using in vitro and in vivo models


Mental retardation (MR) and autism are complex developmental mental disorders characterized by language impairments, social and communicative deficits, and repetitive behaviors, with an estimated prevalence in Europe of 1-2%. Although several genetic alterations have been recognized as causal of mental retardation and autism, the aetiopathogenesis of this disease complex remain largely unknown. The major aim of this project is to develop new experimental models to study mental retardation and autism using neurons derived from the differentiation of induced plurpotent stem (iPS) cells obtained from human patients as well as disease mouse models. The project has the following specific aims: 1) To collect fibroblasts and keratinocytes from mental retardation and autism patients with a clear identified genetic cause. Fibroblast will be also collected from mouse models of MR and autism 2) To reprogram collected fibroblasts and keratinocytes to generate faithful pluripotent stem cells 3) To optimize iPS differentiation into excitatory and inhibitory neurons 4) To characterize iPS derived neurons with regard to synapses morphology, electrophysiology, functional imaging and gene expression 5) To study the ability of iPS-derived neurons to be integrated in a neuronal network system in vitro and in brain areas of mice in vivo 6) To assess lentivirus-mediated site-specific integration of cDNA constructs into defect genes and to gene-correct mutant fibroblasts


Molecular, cellular and genetic approaches, Mental Retardation, Autism

Call topic

Mental Disorders

Proposed runtime

2011 - 2014

Project team

Carlo Sala (Coordinator)
Italy (MOH)
Pierre Billuart
France (ANR)
Eckart Gundelfinger
Germany (BMBF)
Jacek Jaworski
Poland (NCBiR)