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Exploring innovative strategies to restore the synaptic function and socio-cognitive behaviours in a mouse model expressing a recurrent human Fragile X missense mutation
FunderFrench National Research Agency (ANR)
Funder Contribution €496,741.00
DurationFrom 01 Jan 2021
Project codeANR-20-CE16-0006
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Description
Fragile X syndrome is the most common inherited form of intellectual disability and a monogenic cause of autism. This neurodevelopmental disorder results from mutations in the FMR1 gene leading to the lack of expression or abnormal function of the FMRP protein. We demonstrated that FMRP is regulated by the post-translational modification sumoylation, which is essential to its function. Our goal here is to understand how the recurrent Fragile X R138Q mutation, which is close to the SUMO active site of FMRP, affects its regulation. We will use our Knock-in R138Q-FMRP mouse model in which we show alterations in FMRP sumoylation, in AMPAR targeting/trafficking and spine density leading to plasticity defects and altered socio-cognitive behaviours. The aim here is to assess two drugs already used in clinics to correct the molecular, cellular, physiological and abnormal behaviours that are characteristic of the disease.
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Fragile X syndrome is the most common inherited form of intellectual disability and a monogenic cause of autism. This neurodevelopmental disorder results from mutations in the FMR1 gene leading to the lack of expression or abnormal function of the FMRP protein. We demonstrated that FMRP is regulated by the post-translational modification sumoylation, which is essential to its function. Our goal here is to understand how the recurrent Fragile X R138Q mutation, which is close to the SUMO active site of FMRP, affects its regulation. We will use our Knock-in R138Q-FMRP mouse model in which we show alterations in FMRP sumoylation, in AMPAR targeting/trafficking and spine density leading to plasticity defects and altered socio-cognitive behaviours. The aim here is to assess two drugs already used in clinics to correct the molecular, cellular, physiological and abnormal behaviours that are characteristic of the disease.
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