Altered neuroligin expression is involved in social deficits in a mouse model of the fragile X syndrome
Copyright policy )Altered neuroligin expression is involved in social deficits in a mouse model of the fragile X syndrome
The fragile X syndrome (FXS) is the most common form of inherited mental retardation. Caused by a transcriptional silencing of the fragile X mental retardation protein (FMRP), a mRNA binding protein itself, misregulated translation is thought to be the leading cause of the fragile X syndrome. Interestingly, recent results indicated several neuroligin interacting proteins to be affected by this misregulation, including neurexin1 and PSD95, which have also been implicated in autism spectrum disorders. Using co-immunoprecipitation assays and RT-PCR, FMRP is shown to interact with neuroligin1- and 2-mRNA, while no interaction with neuroligin3-mRNA is observed. In line with FMRP's role in translation regulation, Western blot as well as immunohistochemistry analysis reveal changes in protein expression levels suggesting impaired synaptic function. As increasing evidence indicates neuroligin expression to be critical for synapse maturation and function, consequences of impaired neuroligin1 expression in FXS are assessed by overexpressing HA-neuroligin1 in FMR1-/- mice, a model for FXS. Behavioural assessments demonstrate that enhanced neuroligin1 expression improves social behaviour in FMR1-/- mice, whereas no positive effect on learning and memory is seen. These results provide for the first time evidence for an involvement of a neuroligin-neurexin protein network in core symptoms of FXS.
Cell Adhesion Molecules, Neuronal, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Mice, Transgenic, Hippocampus, Aggression, Mice, Inbred C57BL, Fragile X Mental Retardation Protein, Mice, Gene Expression Regulation, Memory, Fragile X Syndrome, Exploratory Behavior, Animals, Immunoprecipitation, Interpersonal Relations, Carrier Proteins, Maze Learning, Disks Large Homolog 4 Protein, Guanylate Kinases
Cell Adhesion Molecules, Neuronal, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Mice, Transgenic, Hippocampus, Aggression, Mice, Inbred C57BL, Fragile X Mental Retardation Protein, Mice, Gene Expression Regulation, Memory, Fragile X Syndrome, Exploratory Behavior, Animals, Immunoprecipitation, Interpersonal Relations, Carrier Proteins, Maze Learning, Disks Large Homolog 4 Protein, Guanylate Kinases
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