A Two Years Longitudinal Study of a Transgenic Huntington Disease Monkey

Anthony W. S. Chan; Yan Xu; Jie Jiang; Tayeb Rahim; Jannet Kocerha; Dongming Zhao; Tim Chi; Heidi Engelhardt; Sean Moran; 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

A Two Years Longitudinal Study of a Transgenic Huntington Disease Monkey

Anthony W. S. Chan, Yan Xu, Jie Jiang, Tayeb Rahim, Jannet Kocerha, Dongming Zhao, Tim Chi, Heidi Engelhardt, Sean Moran, Katherine Larkin, Adam Neumann, Haiying Cheng, Chunxia Li, Katie Nelson, Heather Banta, Stuart M. Zola, Francois Villinger, Jinjing Yang, Claudia M. Testa, Hui MaoXiaodong Zhang, Jocelyne Bachevalier

Biochemistry, Chemistry & Physics

Emory University

Research output: Contribution to journal › Article › peer-review

56 Scopus citations

1 Downloads (Pure)

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.

Original language	American English
Journal	BMC Neuroscience
Volume	15
State	Published - 2014

Disciplines

Chemistry

Keywords

HD
Huntington disease
monkey

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

fulltext.pdfFinal published version, 950 KBLicense: Unspecified

Cite this

@article{2b0f29c1201b4c6a804807ee8cc7fb48,

title = "A Two Years Longitudinal Study of a Transgenic Huntington Disease Monkey",

abstract = " Background: A two-year longitudinal study composed of morphometric MRI measures and cognitive behavioral evaluation was performed on a transgenic Huntington{\textquoteright}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.",

keywords = "HD, Huntington disease, monkey",

author = "Chan, {Anthony W. S.} and Yan Xu and Jie Jiang and Tayeb Rahim and Jannet Kocerha and Dongming Zhao and Tim Chi and Heidi Engelhardt and Sean Moran and Katherine Larkin and Adam Neumann and Haiying Cheng and Chunxia Li and Katie Nelson and Heather Banta and Zola, {Stuart M.} and Francois Villinger and Jinjing Yang and Testa, {Claudia M.} and Hui Mao and Xiaodong Zhang and Jocelyne Bachevalier",

note = "Anthony W. S. Chan, Yan Xu, Jie Jiang, Tayeb Rahim, Jannet Kocerha, Dongming Zhao, Tim Chi, Heidi Engelhardt, Sean Moran, 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, and Jocelyne Bachevalier. {"}A Two Years Longitudinal Study of a Transgenic Huntington Disease Monkey{"} BMC Neuroscience 15.36 (2014). doi:10.1186/1471-2202-15-36 source:http://www.biomedcentral.com/1471-2202/15/36 Available at: http://works.bepress.com/jannet_kocerha/29",

year = "2014",

language = "American English",

volume = "15",

journal = "BMC Neuroscience",

issn = "1471-2202",

publisher = "BioMed Central Ltd",

}

TY - JOUR

T1 - A Two Years Longitudinal Study of a Transgenic Huntington Disease Monkey

AU - Chan, Anthony W. S.

AU - Xu, Yan

AU - Jiang, Jie

AU - Rahim, Tayeb

AU - Kocerha, Jannet

AU - Zhao, Dongming

AU - Chi, Tim

AU - Engelhardt, Heidi

AU - Moran, Sean

AU - Larkin, Katherine

AU - Neumann, Adam

AU - Cheng, Haiying

AU - Li, Chunxia

AU - Nelson, Katie

AU - Banta, Heather

AU - Zola, Stuart M.

AU - Villinger, Francois

AU - Yang, Jinjing

AU - Testa, Claudia M.

AU - Mao, Hui

AU - Zhang, Xiaodong

AU - Bachevalier, Jocelyne

N1 - Anthony W. S. Chan, Yan Xu, Jie Jiang, Tayeb Rahim, Jannet Kocerha, Dongming Zhao, Tim Chi, Heidi Engelhardt, Sean Moran, 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, and Jocelyne Bachevalier. "A Two Years Longitudinal Study of a Transgenic Huntington Disease Monkey" BMC Neuroscience 15.36 (2014). doi:10.1186/1471-2202-15-36 source:http://www.biomedcentral.com/1471-2202/15/36 Available at: http://works.bepress.com/jannet_kocerha/29

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - HD

KW - Huntington disease

KW - monkey

M3 - Article

SN - 1471-2202

VL - 15

JO - BMC Neuroscience

JF - BMC Neuroscience

ER -

A Two Years Longitudinal Study of a Transgenic Huntington Disease Monkey

Abstract

Disciplines

Keywords

UN SDGs

Access to Document

Fingerprint

Cite this