REST overexpression in mice causes deficits in spontaneous locomotion

Li Lu, Anantha Marisetty, Bin Liu, Mohamed Mostafa Kamal, Joy Gumin, Bethany Veo, You Qing Cai, Dina Hamada Kassem, Connie Weng, Mark E. Maynard, Kimberly N. Hood, Gregory N. Fuller, Zhizhong Z. Pan, Matthew D. Cykowski, Pramod K. Dash, Sadhan Majumder

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Overexpression of REST has been implicated in brain tumors, ischemic insults, epilepsy, and movement disorders such as Huntington’s disease. However, owing to the lack of a conditional REST overexpression animal model, the mechanism of action of REST overexpression in these disorders has not been established in vivo. We created a REST overexpression mouse model using the human REST (hREST) gene. Our results using these mice confirm that hREST expression parallels endogenous REST expression in embryonic mouse brains. Further analyses indicate that REST represses the dopamine receptor 2 (Drd2) gene, which encodes a critical nigrostriatal receptor involved in regulating movement, in vivo. Overexpression of REST using Drd2-Cre in adult mice results in increased REST and decreased DRD2 expression in the striatum, a major site of DRD2 expression, and phenocopies the spontaneous locomotion deficits seen upon global DRD2 deletion or specific DRD2 deletion from indirect-pathway medium spiny neurons. Thus, our studies using this mouse model not only reveal a new function of REST in regulating spontaneous locomotion but also suggest that REST overexpression in DRD2-expressing cells results in spontaneous locomotion deficits.

Original languageEnglish (US)
Article number12083
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'REST overexpression in mice causes deficits in spontaneous locomotion'. Together they form a unique fingerprint.

Cite this