A Two Years Longitudinal Study of a Transgenic Huntington Disease Monkey

Overview

Journal BMC Neurosci

Publisher Biomed Central

Specialty Neurology

Date 2014 Mar 4

PMID 24581271

Citations 38

Authors

Anthony Ws Chan

Yan Xu

Jie Jiang

Tayeb Rahim

Dongming Zhao

Jannet Kocerha

Tim Chi

Sean Moran

Heidi Engelhardt

Katherine Larkin

Adam Neumann

Haiying Cheng

Chunxia Li

Katie Nelson

Heather Banta

Stuart M Zola

Francois Villinger

Jinjing Yang

Claudia M Testa

Hui Mao

Xiaodong Zhang

Jocelyne Bachevalier

Affiliations

Soon will be listed here.

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.

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