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

• Type of Material: Article
• Authors: Jannet Kocerha, Yerkes National Primate Research Center; Yuhong Liu, Yerkes National Primate Research Center; David Willoughby, Ocean Ridge Biosciences; Kumaravel Chidamparam, Ocean Ridge Biosciences; Joseph Benito, Ocean Ridge Biosciences; Kate Nelson, Yerkes National Primate Research Center; Yan Xu, Yerkes National Primate Research Center; Tim Chi, Yerkes National Primate Research Center; Heidi Engelhardt, Yerkes National Primate Research Center; Sean Moran, Yerkes National Primate Research Center; Shang-Hsun Yang, Yerkes National Primate Research Center; Shi Hua Li, Emory University; Xiao-Jiang Li, Emory University; Katherine Larkin, Yerkes National Primate Research Center; Adam Neumann, Yerkes National Primate Research Center; Heather Banta, Yerkes National Primate Research Center; Jin Jing Yang, Yerkes National Primate Research Center; Anthony Chan, Emory University
• Language: English
• Date: 2013-08-17
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © 2013 Kocerha et al.; licensee BioMed Central Ltd.
• License: Creative Commons Attribution 2.0 Generic
• Final Published Version (URL): http://dx.doi.org/10.1186/1471-2202-14-88
• Title of Journal or Parent Work: BMC Neuroscience
• ISSN: 1471-2202
• Volume: 14
• Start Page: 88
• End Page: 88
• Grant/Funding Information: Yerkes National Primate Research Center is supported by the National Center for Research Resources P51RR165 and is currently supported by the Office of Research and Infrastructure Program (ORIP)/OD P51OD11132.; This study is supported by grant awarded by the ORIP/NIH (RR018827) and the American Recovery and Reinvestment Act (ARRA) Fund to AWSC.
• Keywords: Animals, Genetically Modified; Humans; Animals; Female; mRNA; Disease Progression; RNA, Messenger; Gene Expression Profiling; Macaca mulatta; Monkeys; Transcriptome; Blood; Longitudinal Studies; Huntington Disease; Disease Models, Animal; Nerve Tissue Proteins; Male
• Research Categories: Biology, Neuroscience; Biology, Genetics; Health Sciences, General

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.