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The hTH-GFP Reporter Rat Model for the Study of Parkinson's Disease

Parkinson disease (PD) is the second leading neurodegenerative disease in the US. As there is no known cause or cure for PD, researchers continue to investigate disease mechanisms and potential new therapies in cell culture and in animal models of PD. In PD, one of the most profoundly affected neuro...

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Autores principales: Iacovitti, Lorraine, Wei, Xiaotao, Cai, Jingli, Kostuk, Eric W., Lin, Ruihe, Gorodinsky, Alexander, Roman, Philip, Kusek, Gretchen, Das, Sonal S., Dufour, Audrey, Martinez, Terina N., Dave, Kuldip D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4251919/
https://www.ncbi.nlm.nih.gov/pubmed/25462571
http://dx.doi.org/10.1371/journal.pone.0113151
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author Iacovitti, Lorraine
Wei, Xiaotao
Cai, Jingli
Kostuk, Eric W.
Lin, Ruihe
Gorodinsky, Alexander
Roman, Philip
Kusek, Gretchen
Das, Sonal S.
Dufour, Audrey
Martinez, Terina N.
Dave, Kuldip D.
author_facet Iacovitti, Lorraine
Wei, Xiaotao
Cai, Jingli
Kostuk, Eric W.
Lin, Ruihe
Gorodinsky, Alexander
Roman, Philip
Kusek, Gretchen
Das, Sonal S.
Dufour, Audrey
Martinez, Terina N.
Dave, Kuldip D.
author_sort Iacovitti, Lorraine
collection PubMed
description Parkinson disease (PD) is the second leading neurodegenerative disease in the US. As there is no known cause or cure for PD, researchers continue to investigate disease mechanisms and potential new therapies in cell culture and in animal models of PD. In PD, one of the most profoundly affected neuronal populations is the tyrosine hydroxylase (TH)-expressing dopaminergic (DA) neurons of the substantia nigra pars compacta (SNpc). These DA-producing neurons undergo degeneration while neighboring DA-producing cells of the ventral tegmental area (VTA) are largely spared. To aid in these studies, The Michael J. Fox Foundation (MJFF) partnered with Thomas Jefferson University and Taconic Inc. to generate new transgenic rat lines carrying the human TH gene promoter driving EGFP using a 11 kb construct used previously to create a hTH-GFP mouse reporter line. Of the five rat founder lines that were generated, three exhibited high level specific GFP fluorescence in DA brain structures (ie. SN, VTA, striatum, olfactory bulb, hypothalamus). As with the hTH-GFP mouse, none of the rat lines exhibit reporter expression in adrenergic structures like the adrenal gland. Line 12141, with its high levels of GFP in adult DA brain structures and minimal ectopic GFP expression in non-DA structures, was characterized in detail. We show here that this line allows for anatomical visualization and microdissection of the rat midbrain into SNpc and/or VTA, enabling detailed analysis of midbrain DA neurons and axonal projections after toxin treatment in vivo. Moreover, we further show that embryonic SNpc and/or VTA neurons, enriched by microdissection or FACS, can be used in culture or transplant studies of PD. Thus, the hTH-GFP reporter rat should be a valuable tool for Parkinson's disease research.
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spelling pubmed-42519192014-12-05 The hTH-GFP Reporter Rat Model for the Study of Parkinson's Disease Iacovitti, Lorraine Wei, Xiaotao Cai, Jingli Kostuk, Eric W. Lin, Ruihe Gorodinsky, Alexander Roman, Philip Kusek, Gretchen Das, Sonal S. Dufour, Audrey Martinez, Terina N. Dave, Kuldip D. PLoS One Research Article Parkinson disease (PD) is the second leading neurodegenerative disease in the US. As there is no known cause or cure for PD, researchers continue to investigate disease mechanisms and potential new therapies in cell culture and in animal models of PD. In PD, one of the most profoundly affected neuronal populations is the tyrosine hydroxylase (TH)-expressing dopaminergic (DA) neurons of the substantia nigra pars compacta (SNpc). These DA-producing neurons undergo degeneration while neighboring DA-producing cells of the ventral tegmental area (VTA) are largely spared. To aid in these studies, The Michael J. Fox Foundation (MJFF) partnered with Thomas Jefferson University and Taconic Inc. to generate new transgenic rat lines carrying the human TH gene promoter driving EGFP using a 11 kb construct used previously to create a hTH-GFP mouse reporter line. Of the five rat founder lines that were generated, three exhibited high level specific GFP fluorescence in DA brain structures (ie. SN, VTA, striatum, olfactory bulb, hypothalamus). As with the hTH-GFP mouse, none of the rat lines exhibit reporter expression in adrenergic structures like the adrenal gland. Line 12141, with its high levels of GFP in adult DA brain structures and minimal ectopic GFP expression in non-DA structures, was characterized in detail. We show here that this line allows for anatomical visualization and microdissection of the rat midbrain into SNpc and/or VTA, enabling detailed analysis of midbrain DA neurons and axonal projections after toxin treatment in vivo. Moreover, we further show that embryonic SNpc and/or VTA neurons, enriched by microdissection or FACS, can be used in culture or transplant studies of PD. Thus, the hTH-GFP reporter rat should be a valuable tool for Parkinson's disease research. Public Library of Science 2014-12-02 /pmc/articles/PMC4251919/ /pubmed/25462571 http://dx.doi.org/10.1371/journal.pone.0113151 Text en © 2014 Iacovitti et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Iacovitti, Lorraine
Wei, Xiaotao
Cai, Jingli
Kostuk, Eric W.
Lin, Ruihe
Gorodinsky, Alexander
Roman, Philip
Kusek, Gretchen
Das, Sonal S.
Dufour, Audrey
Martinez, Terina N.
Dave, Kuldip D.
The hTH-GFP Reporter Rat Model for the Study of Parkinson's Disease
title The hTH-GFP Reporter Rat Model for the Study of Parkinson's Disease
title_full The hTH-GFP Reporter Rat Model for the Study of Parkinson's Disease
title_fullStr The hTH-GFP Reporter Rat Model for the Study of Parkinson's Disease
title_full_unstemmed The hTH-GFP Reporter Rat Model for the Study of Parkinson's Disease
title_short The hTH-GFP Reporter Rat Model for the Study of Parkinson's Disease
title_sort hth-gfp reporter rat model for the study of parkinson's disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4251919/
https://www.ncbi.nlm.nih.gov/pubmed/25462571
http://dx.doi.org/10.1371/journal.pone.0113151
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