例如："lncRNA", "apoptosis", "WRKY"

Control of Huntington's Disease-Associated Phenotypes by the Striatum-Enriched Transcription Factor Foxp2.

Cell Rep. 2017 Dec 05;21(10):2688-2695
Lea J Hachigian 1 , Vitor Carmona 2 , Robert J Fenster 3 , Ruth Kulicke 4 , Adrian Heilbut 5 , Annie Sittler 6 , Luís Pereira de Almeida 2 , Jill P Mesirov 7 , Fan Gao 3 , Eric D Kolaczyk 8 , Myriam Heiman 9
Lea J Hachigian 1 , Vitor Carmona 2 , Robert J Fenster 3 , Ruth Kulicke 4 , Adrian Heilbut 5 , Annie Sittler 6 , Luís Pereira de Almeida 2 , Jill P Mesirov 7 , Fan Gao 3 , Eric D Kolaczyk 8 , Myriam Heiman 9
+ et al

[No authors listed]

Author information
  • 1 Department of Brain and Cognitive Sciences, MIT, Cambridge, MA 02139, USA; Picower Institute for Learning and Memory, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • 2 Center for Neuroscience and Cell Biology (CNC) and Faculty of Pharmacy, The University of Coimbra Rua Larga, 3004-504 Coimbra, Portugal.
  • 3 Picower Institute for Learning and Memory, Cambridge, MA 02139, USA.
  • 4 Picower Institute for Learning and Memory, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • 5 Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Program in Bioinformatics, Boston University, Boston, MA 02215, USA.
  • 6 ICM (Brain and Spine Institute) Pitié-Salpêtrière Hospital, CNRS UMR 7225, 75013 Paris, France.
  • 7 Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • 8 Program in Bioinformatics, Boston University, Boston, MA 02215, USA; Department of Mathematics and Statistics, Boston University, Boston, MA 02215, USA.
  • 9 Department of Brain and Cognitive Sciences, MIT, Cambridge, MA 02139, USA; Picower Institute for Learning and Memory, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: mheiman@mit.edu.

摘要

Alteration of corticostriatal glutamatergic function is an early pathophysiological change associated with Huntington's disease (HD). The factors that regulate the maintenance of corticostriatal glutamatergic synapses post-developmentally are not well understood. Recently, the striatum-enriched transcription factor Foxp2 was implicated in the development of these synapses. Here, we show that, in mice, overexpression of Foxp2 in the adult striatum of two models of HD leads to rescue of HD-associated behaviors, while knockdown of Foxp2 in wild-type mice leads to development of HD-associated behaviors. We note that Foxp2 encodes the longest polyglutamine repeat protein in the human reference genome, and we show that it can be sequestered into aggregates with polyglutamine-expanded mutant Huntingtin protein (mHTT). Foxp2 overexpression in HD model mice leads to altered expression of several genes associated with synaptic function, genes that present additional targets for normalization of corticostriatal dysfunction in HD.

KEYWORDS: Foxp2, Huntington’s disease, corticostriatal synapse, striatum

© 2017 biocloud.net版权所有 ICP证：京10042835号