Impaired Synaptic Plasticity and Motor Learning in Mice with a Point Mutation Implicated in Human Speech Deficits

The most well-described example of an inherited speech and language disorder is that observed in the multigenerational KE family, caused by a heterozygous missense mutation in the FOXP2 gene [1]. Affected individuals are characterized by deficits in the learning and production of complex orofacial m...

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Autores principales: Groszer, Matthias, Keays, David A., Deacon, Robert M.J., de Bono, Joseph P., Prasad-Mulcare, Shweta, Gaub, Simone, Baum, Muriel G., French, Catherine A., Nicod, Jérôme, Coventry, Julie A., Enard, Wolfgang, Fray, Martin, Brown, Steve D.M., Nolan, Patrick M., Pääbo, Svante, Channon, Keith M., Costa, Rui M., Eilers, Jens, Ehret, Günter, Rawlins, J. Nicholas P., Fisher, Simon E.
Formato: Texto
Lenguaje:English
Publicado: Cell Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2917768/
https://www.ncbi.nlm.nih.gov/pubmed/18328704
http://dx.doi.org/10.1016/j.cub.2008.01.060
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author Groszer, Matthias
Keays, David A.
Deacon, Robert M.J.
de Bono, Joseph P.
Prasad-Mulcare, Shweta
Gaub, Simone
Baum, Muriel G.
French, Catherine A.
Nicod, Jérôme
Coventry, Julie A.
Enard, Wolfgang
Fray, Martin
Brown, Steve D.M.
Nolan, Patrick M.
Pääbo, Svante
Channon, Keith M.
Costa, Rui M.
Eilers, Jens
Ehret, Günter
Rawlins, J. Nicholas P.
Fisher, Simon E.
author_facet Groszer, Matthias
Keays, David A.
Deacon, Robert M.J.
de Bono, Joseph P.
Prasad-Mulcare, Shweta
Gaub, Simone
Baum, Muriel G.
French, Catherine A.
Nicod, Jérôme
Coventry, Julie A.
Enard, Wolfgang
Fray, Martin
Brown, Steve D.M.
Nolan, Patrick M.
Pääbo, Svante
Channon, Keith M.
Costa, Rui M.
Eilers, Jens
Ehret, Günter
Rawlins, J. Nicholas P.
Fisher, Simon E.
author_sort Groszer, Matthias
collection PubMed
description The most well-described example of an inherited speech and language disorder is that observed in the multigenerational KE family, caused by a heterozygous missense mutation in the FOXP2 gene [1]. Affected individuals are characterized by deficits in the learning and production of complex orofacial motor sequences underlying fluent speech and display impaired linguistic processing for both spoken and written language [2]. The FOXP2 transcription factor is highly similar in many vertebrate species, with conserved expression in neural circuits related to sensorimotor integration and motor learning [3, 4]. In this study, we generated mice carrying an identical point mutation to that of the KE family, yielding the equivalent arginine-to-histidine substitution in the Foxp2 DNA-binding domain. Homozygous R552H mice show severe reductions in cerebellar growth and postnatal weight gain but are able to produce complex innate ultrasonic vocalizations. Heterozygous R552H mice are overtly normal in brain structure and development. Crucially, although their baseline motor abilities appear to be identical to wild-type littermates, R552H heterozygotes display significant deficits in species-typical motor-skill learning, accompanied by abnormal synaptic plasticity in striatal and cerebellar neural circuits.
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spelling pubmed-29177682010-08-09 Impaired Synaptic Plasticity and Motor Learning in Mice with a Point Mutation Implicated in Human Speech Deficits Groszer, Matthias Keays, David A. Deacon, Robert M.J. de Bono, Joseph P. Prasad-Mulcare, Shweta Gaub, Simone Baum, Muriel G. French, Catherine A. Nicod, Jérôme Coventry, Julie A. Enard, Wolfgang Fray, Martin Brown, Steve D.M. Nolan, Patrick M. Pääbo, Svante Channon, Keith M. Costa, Rui M. Eilers, Jens Ehret, Günter Rawlins, J. Nicholas P. Fisher, Simon E. Curr Biol Report The most well-described example of an inherited speech and language disorder is that observed in the multigenerational KE family, caused by a heterozygous missense mutation in the FOXP2 gene [1]. Affected individuals are characterized by deficits in the learning and production of complex orofacial motor sequences underlying fluent speech and display impaired linguistic processing for both spoken and written language [2]. The FOXP2 transcription factor is highly similar in many vertebrate species, with conserved expression in neural circuits related to sensorimotor integration and motor learning [3, 4]. In this study, we generated mice carrying an identical point mutation to that of the KE family, yielding the equivalent arginine-to-histidine substitution in the Foxp2 DNA-binding domain. Homozygous R552H mice show severe reductions in cerebellar growth and postnatal weight gain but are able to produce complex innate ultrasonic vocalizations. Heterozygous R552H mice are overtly normal in brain structure and development. Crucially, although their baseline motor abilities appear to be identical to wild-type littermates, R552H heterozygotes display significant deficits in species-typical motor-skill learning, accompanied by abnormal synaptic plasticity in striatal and cerebellar neural circuits. Cell Press 2008-03-11 /pmc/articles/PMC2917768/ /pubmed/18328704 http://dx.doi.org/10.1016/j.cub.2008.01.060 Text en © 2008 ELL & Excerpta Medica. https://creativecommons.org/licenses/by/3.0/ Open Access under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/) license
spellingShingle Report
Groszer, Matthias
Keays, David A.
Deacon, Robert M.J.
de Bono, Joseph P.
Prasad-Mulcare, Shweta
Gaub, Simone
Baum, Muriel G.
French, Catherine A.
Nicod, Jérôme
Coventry, Julie A.
Enard, Wolfgang
Fray, Martin
Brown, Steve D.M.
Nolan, Patrick M.
Pääbo, Svante
Channon, Keith M.
Costa, Rui M.
Eilers, Jens
Ehret, Günter
Rawlins, J. Nicholas P.
Fisher, Simon E.
Impaired Synaptic Plasticity and Motor Learning in Mice with a Point Mutation Implicated in Human Speech Deficits
title Impaired Synaptic Plasticity and Motor Learning in Mice with a Point Mutation Implicated in Human Speech Deficits
title_full Impaired Synaptic Plasticity and Motor Learning in Mice with a Point Mutation Implicated in Human Speech Deficits
title_fullStr Impaired Synaptic Plasticity and Motor Learning in Mice with a Point Mutation Implicated in Human Speech Deficits
title_full_unstemmed Impaired Synaptic Plasticity and Motor Learning in Mice with a Point Mutation Implicated in Human Speech Deficits
title_short Impaired Synaptic Plasticity and Motor Learning in Mice with a Point Mutation Implicated in Human Speech Deficits
title_sort impaired synaptic plasticity and motor learning in mice with a point mutation implicated in human speech deficits
topic Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2917768/
https://www.ncbi.nlm.nih.gov/pubmed/18328704
http://dx.doi.org/10.1016/j.cub.2008.01.060
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