Neurocognitive endophenotypes in CGG KI and KO mouse Fmr 1 models of Fragile X-Associated disorders : an analysis of the state of the field

It has become increasingly important that the field of behavioral genetics identifies not only the gross behavioral phenotypes associated with a given mutation, but also the behavioral endophenotypes that scale with the dosage of the particular mutation being studied. Over the past few years, studies evaluating the effects of the polymorphic CGG trinucleotide repeat on the gene underlying Fragile X-Associated Disorders have reported FMR1 preliminary evidence for a behavioral endophenotype in human Fragile X Premutation carrier populations as well as the CGG knock-in (KI) mouse model. More recently, the behavioral experiments used to test the CGG KI mouse model have been extended to the knock-out (KO) mouse model. When Fmr1 combined, these data provide compelling evidence for a clear neurocognitive endophenotype in the mouse models of Fragile X-Associated Disorders such that behavioral deficits scale predictably with genetic dosage. Similarly, it appears that the CGG KI mouse effectively models the histopathology in Fragile X-Associated Disorders across CGG repeats well into the full mutation range, resulting in a reliable histopathological endophenotype. These endophenotypes may influence future research directions into treatment strategies for not only Fragile X Syndrome, but also the Fragile X Premutation and Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS). Michael R. Hunsaker ( ) Corresponding author: Mrhunsaker@icloud.com Hunsaker MR. How to cite this article: Neurocognitive endophenotypes in CGG KI and KO mouse models of Fragile X-Associated Fmr1 2013, :287 (doi: disorders: an analysis of the state of the field [version 1; referees: 2 approved] F1000Research 2 ) 10.12688/f1000research.2-287.v1 © 2013 Hunsaker MR. This is an open access article distributed under the terms of the , which Copyright: Creative Commons Attribution Licence permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Data associated with the article are available under the terms of the (CC0 1.0 Public domain dedication). Creative Commons Zero "No rights reserved" data waiver The author(s) declared that no grants were involved in supporting this work. Grant information: Competing interests: No competing interests were disclosed. 27 Dec 2013, :287 (doi: ) First published: 2 10.12688/f1000research.2-287.v1 Referee Status: