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The hTH-GFP reporter rat model for the study of Parkinson's disease.

作者信息

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

机构信息

Farber Institute of Neurosciences, Department of Neuroscience, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.

Taconic Farms, Inc., Hudson, New York, United States of America.

出版信息

PLoS One. 2014 Dec 2;9(12):e113151. doi: 10.1371/journal.pone.0113151. eCollection 2014.


DOI:10.1371/journal.pone.0113151
PMID:25462571
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4251919/
Abstract

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.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c53/4251919/3abdf06515ad/pone.0113151.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c53/4251919/d6be29a7c6aa/pone.0113151.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c53/4251919/5dd5f520677f/pone.0113151.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c53/4251919/d7409dcbeace/pone.0113151.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c53/4251919/e47932755668/pone.0113151.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c53/4251919/92715ae6b028/pone.0113151.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c53/4251919/80ee451bff6d/pone.0113151.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c53/4251919/3abdf06515ad/pone.0113151.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c53/4251919/d6be29a7c6aa/pone.0113151.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c53/4251919/5dd5f520677f/pone.0113151.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c53/4251919/d7409dcbeace/pone.0113151.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c53/4251919/e47932755668/pone.0113151.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c53/4251919/92715ae6b028/pone.0113151.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c53/4251919/80ee451bff6d/pone.0113151.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c53/4251919/3abdf06515ad/pone.0113151.g007.jpg

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[6]
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[8]
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[9]
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[10]
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本文引用的文献

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