|Role of the FMR1 Gene
by Richard Paylor, 2/1/2005
To understand the role of the FMR1 gene and its product FMRP in central nervous system function, researchers have engineered a mouse that lacks FMRP (the FMR1 knockout mouse). Although several laboratories have found that these mice are hyperactive, have abnormal startle responses, and are prone to seizures, there appears to be no consistent learning and memory impairment in the mice. This has hampered efforts to identify and test therapeutic interventions for the cognitive impairments associated with Fragile X.
We have recently discovered that FMR1 knockout mice have a profound impairment on a specific test oflearning: the lever press escape/avoidance test. Performance in this test can be associated with changes in two neuropeptides: brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in various brain regions.
Our project has three goals:
1.To better understand this learning impairment
2. To determine whether there is a relationship between BDNF and NGF levels and the avoidance learning of FMR1 KO mice.
3.To rescue the leverpress avoidance learning impairment with MPEP and/or ampakines, while monitoring changes in BDNF and NGF levels. With this robust learning impairment in mice, we believe we are in a unique position to better understand the role of FMRP in learning and memory and to evaluate potential treatments.