FACL4 AND MENTAL RETARDATION: CELLULAR AND MOUSE MODELS

  • 3 Years 2004/2007
  • 180.000€ Total Award
Mental retardation (MR) is the most frequent cause of serious handicap in humans with an estimated total prevalence of 1-1,5% in the general population. It is calculated that X-linked MR (XLMR) may account for about 20-25% of mentally retarded males. Up to now, 15 genes have been found involved in non-specific XLMR, were mental retardation is the only consistent finding. Among them, FACL4 gene was recently identified by our group. Knowledge on the pathogenic mechanisms linking FACL4 mutations to MR is very limited. To define such mechanisms we plan to characterize FACL4 expression in neurons and in lymphoblastoid cells and to define its subcellular localization. In addition, proteins interacting with FACL4 will be characterized. A human knock-out cellular model and a mouse knock-out model will be generated. The cellular model will be generated employing neuronal cell lines and it will allow to evaluate the consequences of FACL4 absence directly in neurons. With this model we will analyze changes in: (1) cell morphology; (2) membrane protein and lipid composition; (3) gene expression. The mouse model will be employed to evaluate general brain histology and behavior. In addition, primary neurons will be isolated from knock-out mice and normal siblings. These cells will be employed for the analysis of cell morphology, membrane protein and lipid composition and gene expression. These analyses will be important to validate the results obtained with the cellular model. A better understanding of the function of FACL4 gene in the cell will be essential to shed light not only on the pathogenic mechanisms leading to MR but also on the mechanisms of normal brain function.

Scientific Publications

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