title: The hTH-GFP reporter rat model for the study of Parkinson's disease.
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.
authors.affiliation: Farber Institute of Neurosciences, Department of Neuroscience, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Iacovitti
authors.affiliation: Farber Institute of Neurosciences, Department of Neuroscience, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Xiaotao
authors.initials: X
authors.lastname: Wei
authors.affiliation: Farber Institute of Neurosciences, Department of Neuroscience, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Jingli
authors.initials: J
authors.lastname: Cai
authors.affiliation: Farber Institute of Neurosciences, Department of Neuroscience, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Eric W
authors.initials: EW
authors.lastname: Kostuk
authors.affiliation: Farber Institute of Neurosciences, Department of Neuroscience, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Ruihe
authors.initials: R
authors.lastname: Lin
authors.affiliation: Taconic Farms, Inc., Hudson, New York, United States of America.
authors.forename: Alexander
authors.initials: A
authors.lastname: Gorodinsky
authors.affiliation: Taconic Farms, Inc., Hudson, New York, United States of America.
authors.forename: Philip
authors.initials: P
authors.lastname: Roman
authors.affiliation: Taconic Farms, Inc., Hudson, New York, United States of America.
authors.forename: Gretchen
authors.initials: G
authors.lastname: Kusek
authors.affiliation: The Michael J. Fox Foundation for Parkinson's Research, New York, New York, United States of America.
authors.forename: Sonal S
authors.initials: SS
authors.lastname: Das
authors.affiliation: The Michael J. Fox Foundation for Parkinson's Research, New York, New York, United States of America.
authors.forename: Audrey
authors.initials: A
authors.lastname: Dufour
authors.affiliation: The Michael J. Fox Foundation for Parkinson's Research, New York, New York, United States of America.
authors.forename: Terina N
authors.initials: TN
authors.lastname: Martinez
authors.affiliation: The Michael J. Fox Foundation for Parkinson's Research, New York, New York, United States of America.
authors.forename: Kuldip D
authors.initials: KD
authors.lastname: Dave
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000235:genetics / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D051379:Mice; D009830:Olfactory Bulb / Q000378:metabolism; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D065842:Pars Compacta / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics
chemical_list: C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine