Open Access Highly Accessed Research article

Longitudinal transcriptomic dysregulation in the peripheral blood of transgenic Huntington’s disease monkeys

Jannet Kocerha124, Yuhong Liu1, David Willoughby3, Kumaravel Chidamparam3, Joseph Benito3, Kate Nelson1, Yan Xu12, Tim Chi1, Heidi Engelhardt1, Sean Moran1, Shang-Hsun Yang1, Shi-Hua Li2, Xiao-Jiang Li2, Katherine Larkin1, Adam Neumann1, Heather Banta1, Jin Jing Yang1 and Anthony WS Chan12*

Author Affiliations

1 Department of Neuropharmacology and Neurologic Disease, Yerkes National Primate Research Center, 954 Gatewood Rd., N.E, Atlanta, GA 30329, USA

2 Department of Human Genetics, Emory University School of Medicine, 615 Michael St. Whitehead Building, Atlanta, GA 30322, USA

3 Ocean Ridge Biosciences, 10475 Riverside Drive, Suite 1, Palm Beach Gardens, FL 33410, USA

4 Current address: Department of Chemistry, Georgia Southern University, Statesboro, GA 30458, USA

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BMC Neuroscience 2013, 14:88  doi:10.1186/1471-2202-14-88

Published: 17 August 2013

Abstract

Background

Huntington’s Disease (HD) is a progressive neurodegenerative disorder caused by an expansion in the polyglutamine (polyQ) region of the Huntingtin (HTT) gene. The clinical features of HD are characterized by cognitive, psychological, and motor deficits. Molecular instability, a core component in neurological disease progression, can be comprehensively evaluated through longitudinal transcriptomic profiling. Development of animal models amenable to longitudinal examination enables distinct disease-associated mechanisms to be identified.

Results

Here we report the first longitudinal study of transgenic monkeys with genomic integration of various lengths of the human HTT gene and a range of polyQ repeats. With this unique group of transgenic HD nonhuman primates (HD monkeys), we profiled over 47,000 transcripts from peripheral blood collected over a 2 year timespan from HD monkeys and age-matched wild-type control monkeys.

Conclusions

Messenger RNAs with expression patterns which diverged with disease progression in the HD monkeys considerably facilitated our search for transcripts with diagnostic or therapeutic potential in the blood of human HD patients, opening up a new avenue for clinical investigation.

Keywords:
Transcriptome; Huntington’s disease; Longitudinal; Monkeys; Blood; mRNA