Yong-Seok Lee, Dan Ehninger, Miou Zhou, Jun-Young Oh, Minkyung Kang, Chuljung Kwak, Hyun-Hee Ryu, Delana Butz, Toshiyuki Araki, Ying Cai, J Balaji, Yoshitake Sano, Christine I Nam, Hyong Kyu Kim, Bong-Kiun Kaang, Corinna Burger, Benjamin G Neel, Alcino J Silva
In Noonan syndrome (NS) 30-50% of subjects show cognitive deficits of unknown etiology and with no known treatment. Here, we report that knock-in mice expressing either of two NS-associated mutations in Ptpn11, which encodes the nonreceptor protein tyrosine phosphatase Shp2, show hippocampal-dependent impairments in spatial learning and deficits in hippocampal long-term potentiation (LTP). In addition, viral overexpression of an NS-associated allele PTPN11(D61G) in adult mouse hippocampus results in increased baseline excitatory synaptic function and deficits in LTP and spatial learning, which can be reversed by a mitogen-activated protein kinase kinase (MEK) inhibitor...
December 2014: Nature Neuroscience