Neurocognitive endophenotypes in CGG KI and Fmr1 KO mouse models of Fragile X-Associated disorders: an analysis of the state of the field [v1; ref status: indexed, http://f1000r.es/2mk]

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, studie...

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Main Author: Michael R. Hunsaker
Format: Article
Language:English
Published: F1000 Research Ltd 2013-12-01
Series:F1000Research
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Online Access:http://f1000research.com/articles/2-287/v1
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spelling doaj-599e218c1cb3469ea4d7cf6326f3cf5d2020-11-25T03:20:37ZengF1000 Research LtdF1000Research2046-14022013-12-01210.12688/f1000research.2-287.v13404Neurocognitive endophenotypes in CGG KI and Fmr1 KO mouse models of Fragile X-Associated disorders: an analysis of the state of the field [v1; ref status: indexed, http://f1000r.es/2mk]Michael R. Hunsaker0Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, UT, USAIt 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 FMR1 gene underlying Fragile X-Associated Disorders have reported 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 Fmr1 knock-out (KO) mouse model. When 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).http://f1000research.com/articles/2-287/v1Animal GeneticsBehavioral NeuroscienceCognitive NeuroscienceMotor Systems
collection DOAJ
language English
format Article
sources DOAJ
author Michael R. Hunsaker
spellingShingle Michael R. Hunsaker
Neurocognitive endophenotypes in CGG KI and Fmr1 KO mouse models of Fragile X-Associated disorders: an analysis of the state of the field [v1; ref status: indexed, http://f1000r.es/2mk]
F1000Research
Animal Genetics
Behavioral Neuroscience
Cognitive Neuroscience
Motor Systems
author_facet Michael R. Hunsaker
author_sort Michael R. Hunsaker
title Neurocognitive endophenotypes in CGG KI and Fmr1 KO mouse models of Fragile X-Associated disorders: an analysis of the state of the field [v1; ref status: indexed, http://f1000r.es/2mk]
title_short Neurocognitive endophenotypes in CGG KI and Fmr1 KO mouse models of Fragile X-Associated disorders: an analysis of the state of the field [v1; ref status: indexed, http://f1000r.es/2mk]
title_full Neurocognitive endophenotypes in CGG KI and Fmr1 KO mouse models of Fragile X-Associated disorders: an analysis of the state of the field [v1; ref status: indexed, http://f1000r.es/2mk]
title_fullStr Neurocognitive endophenotypes in CGG KI and Fmr1 KO mouse models of Fragile X-Associated disorders: an analysis of the state of the field [v1; ref status: indexed, http://f1000r.es/2mk]
title_full_unstemmed Neurocognitive endophenotypes in CGG KI and Fmr1 KO mouse models of Fragile X-Associated disorders: an analysis of the state of the field [v1; ref status: indexed, http://f1000r.es/2mk]
title_sort neurocognitive endophenotypes in cgg ki and fmr1 ko mouse models of fragile x-associated disorders: an analysis of the state of the field [v1; ref status: indexed, http://f1000r.es/2mk]
publisher F1000 Research Ltd
series F1000Research
issn 2046-1402
publishDate 2013-12-01
description 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 FMR1 gene underlying Fragile X-Associated Disorders have reported 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 Fmr1 knock-out (KO) mouse model. When 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).
topic Animal Genetics
Behavioral Neuroscience
Cognitive Neuroscience
Motor Systems
url http://f1000research.com/articles/2-287/v1
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