A two years longitudinal study of a transgenic Huntington disease monkey

• Type of Material: Article
• Authors: Anthony Chan, Emory University; Yan Xu, Emory University; Jie Jiang, Emory University; Tayeb Rahim, Emory University; Dongming Zhao, Emory University; Jannet Kocerha, Emory University; Tim Chi, Emory University; Sean Moran, Emory University; Heidi Engelhardt, Emory University; Katherine Larkin, Emory University; Adam Neumann, Emory University; Haiying Cheng, Emory University; Chunxia Li, Emory University; Katie Nelson, Emory University; Heather Banta, Emory University; Stuart M Zola, Emory University; Francois Villinger, Emory University; Jin Jing Yang, Emory University; Claudia M Testa, Emory University; Hui Mao, Emory University; Xiaodong Zhang, Emory University; Jocelyne Bachevalier, Emory University
• Language: English
• Date: 2014
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © 2014 Chan et al.; licensee BioMed Central Ltd.
• License: Creative Commons Attribution 2.0 Generic
• Final Published Version (URL): http://www.biomedcentral.com/1471-2202/15/36
• Title of Journal or Parent Work: BMC Neuroscience
• ISSN: 1471-2202
• Volume: 15
• Issue: 36
• Grant/Funding Information: This study is supported by grants awarded by the ORIP/NIH (RR018827) to AWSC and in part by the NIMH (MH58846) to JB.
• Research Categories: Health Sciences, Radiology; Health Sciences, General

Abstract

Background A two-year longitudinal study composed of morphometric MRI measures and cognitive behavioral evaluation was performed on a transgenic Huntington’s disease (HD) monkey. rHD1, a transgenic HD monkey expressing exon 1 of the human gene encoding huntingtin (HTT) with 29 CAG repeats regulated by a human polyubiquitin C promoter was used together with four age-matched wild-type control monkeys. This is the first study on a primate model of human HD based on longitudinal clinical measurements. Results Changes in striatal and hippocampal volumes in rHD1 were observed with progressive impairment in motor functions and cognitive decline, including deficits in learning stimulus-reward associations, recognition memory and spatial memory. The results demonstrate a progressive cognitive decline and morphometric changes in the striatum and hippocampus in a transgenic HD monkey. Conclusions This is the first study on a primate model of human HD based on longitudinal clinical measurements. While this study is based a single HD monkey, an ongoing longitudinal study with additional HD monkeys will be important for the confirmation of our findings. A nonhuman primate model of HD could complement other animal models of HD to better understand the pathogenesis of HD and future development of diagnostics and therapeutics through longitudinal assessment.