Social deficits in mouse models of Neurofibromatosis type 1 and Legius syndrome

Abstract

Event Abstract Back to Event Social deficits in mouse models of Neurofibromatosis type 1 and Legius syndrome Sarah C. Borrie1*, Ellen Plasschaert1, Ype Elgersma2, Steven A. Kushner2, Eric Legius1 and Hilde Brems1 1 KU Leuven, Department of Human Genetics, Belgium 2 Erasmus Medical Center, Netherlands Neurofibromatosis type 1 (NF1) and Legius syndrome are neuro-cardio-facial-cutaneous (NCFC) disorders stemming from mutations in the RAS – MAPK pathway, in the NF1 and SPRED1 genes respectively. NF1 is a RAS-GAP protein, negatively regulating activation of RAS, while SPRED1 acts further downstream in the RAS-MAPK pathway, negatively regulating the activation of RAF1 by RAS. Common to these disorders are neurological problems including cognitive deficits and behavioral problems. Patients with NF1 exhibit deficits in memory and executive functioning, and have a high incidence of autism sprectrum disorder (ASD). Legius syndrome patients present a milder cognitive phenotype compared to NF1 patients, and ADHD and attentional problems are also reported. A mouse model of NF1, Nf1+/-, exhibits spatial memory and attentional impairments consistent with the human disorder, and the Spred1-/- mouse model for Legius syndrome also demonstrates spatial learning deficits. However, it is not known whether these models also recapitulate ASD-like symptoms seen in NF1. To further study this phenomenon, we studied social behaviors in Nf1+/- mice and Spred1-/- and Spred1+/- mice, to ask if social deficits are observed in these models, and whether any observed deficits can be rescued. Spred1-/- and Spred1+/- mice displayed abnormal social behavior in the automated tube test. Both genotypes won more encounters against wildtype littermates than expected by chance, indicative of disrupted social behavior. Other social behaviors were also impaired in Spred1-/- mice, including nesting, an intrinsic social behavior. Social deficits in Spred1-/- could be reversed in adult mice by inhibiting the RAS-MAPK pathway, suggesting that RAS – MAPK pathway overactivation underlies altered social behavior in this model. Studies in Nf1+/- mice show that similar social deficits are observed in the automated tube test. Other social behaviors are also being tested, and the role of RAS –MAPK signaling in mediating this phenotype in Nf1+/- is being investigated with pharmacological studies. Collectively these findings suggest that deficits in social behaviors that are core symptoms of NCFC syndromes can be reliably modelled in mouse models of NF1 and Legius syndrome, and that disruptions in RAS-MAPK signaling are important for these behavior alterations. Keywords: RAS-MAPK, NF1, Legius syndrome, ASD, Social Behaviour Conference: 12th National Congress of the Belgian Society for Neuroscience, Gent, Belgium, 22 May - 22 May, 2017. Presentation Type: Poster Presentation Topic: Disorders of the Nervous System Citation: Borrie SC, Plasschaert E, Elgersma Y, Kushner SA, Legius E and Brems H (2019). Social deficits in mouse models of Neurofibromatosis type 1 and Legius syndrome. Front. Neurosci. Conference Abstract: 12th National Congress of the Belgian Society for Neuroscience. doi: 10.3389/conf.fnins.2017.94.00027 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 24 Apr 2017; Published Online: 25 Jan 2019. * Correspondence: Dr. Sarah C Borrie, KU Leuven, Department of Human Genetics, Leuven, Belgium, sarah.borrie@kuleuven.be Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Sarah C Borrie Ellen Plasschaert Ype Elgersma Steven A Kushner Eric Legius Hilde Brems Google Sarah C Borrie Ellen Plasschaert Ype Elgersma Steven A Kushner Eric Legius Hilde Brems Google Scholar Sarah C Borrie Ellen Plasschaert Ype Elgersma Steven A Kushner Eric Legius Hilde Brems PubMed Sarah C Borrie Ellen Plasschaert Ype Elgersma Steven A Kushner Eric Legius Hilde Brems Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.