Neurofibromatosis type 1 (NF1) is a single-gene disorder with multiple somatic and behavioral phenotypes. NF1 and other related disorders, including Noonan syndrome, Costello syndrome, LEOPARD syndrome, and CFC syndrome are caused by gain-of-function mutations in various components of the Ras-MAPK signaling pathway and are therefore known as rasopathies. Individuals affected with any one of these disorders exhibit various cognitive problems such as learning disabilities and mental retardation. Many of the cognitive phenotypes observed in the rasopathies can be modeled in animal models, including mice. Studies in these animal models have played an important role in understanding the molecular and cellular mechanisms underlying the cognitive deficits associated with NF1 and other rasopathies. For example, studies in mouse models of NF1 have shown that increased inhibition and subsequent disruptions in synaptic plasticity caused by increased Ras signaling are responsible for cognitive deficits in this condition. Based on these mechanistic findings, pharmacological interventions that decrease Ras signaling have been shown to be able to rescue deficits in both synaptic plasticity and behavior in a mouse model of NF1, and these have inspired current clinical trials. In this chapter, we shall review molecular, cellular, and behavioral studies of mouse models of NF1 and other rasopathies, as well as efforts to use these results to develop treatments for this class of conditions.
|Title of host publication||Neurofibromatosis Type 1|
|Subtitle of host publication||Molecular and Cellular Biology|
|Publisher||Springer-Verlag Berlin Heidelberg|
|Number of pages||20|
|ISBN (Print)||3642328636, 9783642328633|
|State||Published - 1 Aug 2012|