REST overexpression in mice causes deficits in spontaneous locomotion

Authors

Li Lu, University of Texas MD Anderson Cancer Center
Anantha Marisetty, University of Texas MD Anderson Cancer Center
Bin Liu, University of Texas MD Anderson Cancer Center
Mohamed M. Kamal, The British University in EgyptFollow
Joy Gumin, University of Texas MD Anderson Cancer Center
Bethany Veo, University of Texas MD Anderson Cancer Center
You Qing Cai, University of Texas MD Anderson Cancer Center
Dina Hamada Kassem, University of Texas MD Anderson Cancer Center
Connie Weng, University of Texas MD Anderson Cancer Center
Mark E. Maynard, University of Texas System
Kimberly N. Hood, University of Texas System
Gregory N. Fuller, University of Texas MD Anderson Cancer Center
Zhizhong Z. Pan, University of Texas MD Anderson Cancer Center
Matthew D. Cykowski, Methodist Hospital Houston
Pramod K. Dash, University of Texas System
Sadhan Majumder, University of Texas MD Anderson Cancer Center

Document Type

Article

Publication Date

12-1-2018

Abstract

© 2018, The Author(s). 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.

Recommended Citation

Lu, Li; Marisetty, Anantha; Liu, Bin; Kamal, Mohamed M.; Gumin, Joy; Veo, Bethany; Cai, You Qing; Kassem, Dina Hamada; Weng, Connie; Maynard, Mark E.; Hood, Kimberly N.; Fuller, Gregory N.; Pan, Zhizhong Z.; Cykowski, Matthew D.; Dash, Pramod K.; and Majumder, Sadhan, "REST overexpression in mice causes deficits in spontaneous locomotion" (2018). Pharmacy. 315.
https://buescholar.bue.edu.eg/pharmacy/315