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

BMC Neuroscience

Anthony WS Chan³  Jin Jing Yang²  Heather Banta²  Adam Neumann²  Katherine Larkin²  Xiao-Jiang Li³  Shi-Hua Li³  Shang-Hsun Yang²  Sean Moran²  Heidi Engelhardt²  Tim Chi²  Yan Xu³  Kate Nelson²  Joseph Benito⁴  Kumaravel Chidamparam⁴  David Willoughby⁴  Yuhong Liu²  Jannet Kocerha¹ 

[1] Current address: Department of Chemistry, Georgia Southern University, Statesboro, GA 30458, USA;Department of Neuropharmacology and Neurologic Disease, Yerkes National Primate Research Center, 954 Gatewood Rd., N.E, Atlanta, GA 30329, USA;Department of Human Genetics, Emory University School of Medicine, 615 Michael St. Whitehead Building, Atlanta, GA 30322, USA;Ocean Ridge Biosciences, 10475 Riverside Drive, Suite 1, Palm Beach Gardens, FL 33410, USA

关键词: mRNA;    Blood;    Monkeys;    Longitudinal;    Huntington’s disease;    Transcriptome;   

Others  :  1140148
DOI  :  10.1186/1471-2202-14-88

 received in 2013-04-10, accepted in 2013-08-14,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Kocerha et al.; licensee BioMed Central Ltd.

【 图 表 】

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